ORCID Profile
0000-0002-3489-7595
Current Organisations
Monash University Central Clinical School
,
The Alfred Hospital
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Publisher: Cold Spring Harbor Laboratory
Date: 20-11-2020
DOI: 10.1101/2020.11.17.20233544
Abstract: Lasting immunity to SARS-CoV-2 following infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. To determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. Recombinant spike receptor binding domain (RBD) and nucleocapsid protein (NCP) were produced for ELISA-based serology, and biotinylated for fluorescent tetramer generation to identify SARS-CoV-2-specific Bmem cells by flow cytometry with a panel of 13 mAbs. 36 blood s les were obtained from 25 COVID-19 patients (11 paired) between 4-242 days post-symptom onset for detection of neutralizing antibodies, IgG serology and flow cytometry. The recombinant RBD and NCP were specifically recognized by serum IgG in all patients and reactivity declined days post-symptom onset. All patients had detectable RBD- and NCP-specific Bmem cells at 8.23-267.6 cells/ml of blood (0.004-0.13% of B cells) regardless of s ling time. RBD- and NCP-specific Bmem cells predominantly expressed IgM or IgG1, with the latter formed slightly later than the former. RBD-specific IgG + Bmem were predominantly CD27 + , and numbers significantly correlated with circulating follicular helper T cell numbers. RBD- and NCP-specific Bmem cells persisted for 8 months, indicating that the decline in serum antibodies after 1 month does not indicate waning of immunity but a contraction of the immune response. Flowcytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term functional immunity following infection or vaccination for COVID-19.
Publisher: S. Karger AG
Date: 1989
DOI: 10.1159/000234750
Abstract: We have studied a number of aspects of the interrelationship between T lymphocytes and allergic inflammation. Using monoclonal antibodies and immunocytochemistry we have observed significant infiltration by CD3 sup + /sup /CD4 sup + /sup T lymphocytes together with evidence of T cell activation in the allergen-induced late-phase skin reaction in human atopic subjects. These changes were accompanied by eosinophil infiltration and activation. Activated T cells were also detected in the blood of patients with acute severe asthma. The role of T lymphocytes in granulocyte chemotaxis and activation was also explored, using recombinant human lymphokines, and we have identified and characterized two lymphokines which have specific effects upon neutrophils.
Publisher: Elsevier BV
Date: 04-1992
DOI: 10.1016/0091-6749(92)90431-Z
Abstract: Single motor unit potentials were recorded with small bipolar wires from intact masseter muscles in the adult man and a detailed parametric analysis of the effects of muscle vibration on motor unit discharges was carried out. 2. When the vibration litude was kept constant, each unit started firing at a definite threshold of vibration frequency. With higher frequencies the rate of firing rapidly reached a maximum. Units recruited at higher frequencies presented a lower maximum rate of firing. 3. When the vibration frequency was kept constant, each masseter unit discharged at a definite threshold of vibration litude. With higher litudes the unit quickly reached a maximum rate of discharge. Units with a higher frequency threshold tended to also present a higher litude threshold. Motor unit "excitability" curves could be plotted using the combined threshold conditions for frequency and litude of applied vibrations. 4. With a given parametric set of vibration, the units only started firing at a given delay after the onset of vibration. The delay was quite different for different units and it increased considerably, sometimes by several seconds, when the vibration litude was made smaller. 5. In all the experimental conditions tested, and even when the unit discharge did not start until several seconds after vibration onset, the unit potential presented a close and highly consistent temporal relation to the vibration cycles. The slow recruitment process is thought to involve a polysynaptic excitatory mechanism which progressively depolarizes the masseter motoneurones close to their threshold, the actual firing being triggered by monosynaptic excitatory post-synaptic potentials from I(a) afferents, hence the small latency jitter recorded. This special pattern of tonic vibration reflex in jaw-closing muscles in man may result from the lack of reciprocal inhibition from the jaw-opening muscles.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Wiley
Date: 23-10-2017
Publisher: Wiley
Date: 13-01-2011
DOI: 10.1111/J.1365-2222.2010.03670.X
Abstract: Grass pollens are major triggers of allergic rhinitis and asthma, but the immunological relationships between pollen allergens of the subtropical Bahia grass, Paspalum notatum, and temperate grasses are unresolved. To assess serum IgE cross-reactivity between subtropical P. notatum and temperate Lolium perenne (Ryegrass) pollen allergens. Serum IgE reactivities of grass pollen-allergic patients with P. notatum, L. perenne and Cynodon dactylon (Bermuda grass) pollen extracts and their respective purified group 1 allergens, Pas n 1, Lol p 1 and Cyn d 1, were compared by immunoblotting, ELISA and basophil activation. In a cohort of 51 patients from a temperate region, a high frequency of IgE reactivity with each grass pollen was detected, but reactivity with L. perenne pollen was substantially greater than with P. notatum and C. dactylon pollen. Similarly, serum IgE reactivity with Lol p 1 was greater than with Pas n 1 or Cyn d 1. For seven of eight sera studied in detail, asymmetric serum IgE cross-reactivity was observed L. perenne pollen inhibited IgE reactivity with P. notatum pollen but not the converse, and IgE reactivity with Pas n 1 was inhibited by Lol p 1 but IgE reactivity with Lol p 1 was not inhibited by Pas n 1 or Cyn d 1. Importantly, P. notatum pollen and Pas n 1 activated basophils in grass pollen-allergic patients from a temperate region, although stimulation was greater by pollen of L. perenne than P. notatum or C. dactylon, and by Lol p 1 than Pas n 1 or Cyn d 1. In contrast, a cohort of 47 patients from a subtropical region showed similar IgE reactivity with P. notatum and L. perenne pollen, and reciprocal cross-inhibition of IgE reactivity between L. perenne and P. notatum. Pollen allergens of the subtropical P. notatum, including Pas n 1, show clinically relevant IgE cross-reactivity with pollen allergens of L. perenne but also species-specific IgE reactivity.
Publisher: Wiley
Date: 1992
Publisher: Frontiers Media SA
Date: 22-12-2017
Publisher: Wiley
Date: 08-2009
Publisher: Wiley
Date: 04-11-2019
DOI: 10.1111/ALL.14073
Abstract: While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen‐specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T‐cell function and increased allergen‐specific IgG 4 , yet little is known about the effect on the memory B‐cell compartment. We aimed to examine the effects of AIT on the IgE‐ and IgG subclass‐expressing memory B cells. We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP Lolium perenne ). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE + and IgG + memory B cells and allergen‐specific Ig levels. SLIT increased RGP‐specific serum IgG 2 and IgG 4 , as well as the frequencies of IgG 2 + and IgG 4 + memory B cells, whereas no effect was observed on the IgE + memory B‐cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement. Our data provide evidence for immunological effects of SLIT on B‐cell memory. Skewing responses toward IgG 2 and IgG 4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses.
Publisher: Wiley
Date: 12-1993
DOI: 10.1111/J.1365-2362.1993.TB00729.X
Abstract: CD4+ T-lymphocytes induce and regulate allergic inflammatory responses to common environmental aeroallergens derived from Dermatophagoides spp. (house dust mite, HDM), which cause clinical symptoms in approximately 10% of the population. Definition of the molecular structure of HDM proteins combined with the ability to isolate monoclonal populations of human CD4+ T-cells representative of the 'interleukin-4 (IL-4) dominant' functional phenotype, which support immunoglobulin E (IgE) synthesis, has allowed T-cell recognition of HDM to be examined in detail. The results of these investigations demonstrated extensive heterogeneity in both the antigen and HLA class II restriction specificity of the HDM reactive T-cell repertoire. Furthermore, long-lived clones of T-cells with oligoclonality in T-cell antigen receptor (TcR) usage, driven by chronic stimulation with HDM, have been identified in human peripheral blood. The presentation of specific peptides and superantigens under conditions that induce T-cell non-responsiveness has provided an in vitro model for analysing the mechanisms of CD4+ T-cell targeted immunotherapy. It appears that the mechanisms underlying T-cell anergy are accompanied by a transient downregulation of TcR and CD28 and mediated by a shift in the cytokine profile from that of the 'IL-4 dominant' to the 'interferon-gamma (IFN-gamma) dominant' functional phenotype of CD4+ T-cells. In parallel, using a murine model, it has been demonstrated that administration of an immunodominant peptide via the mucosal surfaces of the respiratory and alimentary tracts may tolerize an established response to intact HDM proteins. The potential application of these models in the development of novel approaches to immunotherapy is discussed.
Publisher: Portland Press Ltd.
Date: 08-1995
DOI: 10.1042/BST0230660
Publisher: Oxford University Press (OUP)
Date: 1991
Abstract: A failure of T lymphocytes to produce interleukin 2 (IL-2) on restimulation may, in part, account for the specific unresponsiveness that accompanies incomplete activation. The evidence to support this has been derived predominantly from the investigation of the molecular basis of anergy in murine type 1 T cells. In this study, the effects of different tolerogenic signals delivered by specific peptide or Staphylococcus aureus enterotoxin on the ability of antigen-specific human T cells to produce lymphokines, both in the induction phase and in established antigen-specific non-responsiveness, have been examined. Although T cell proliferation was decreased by supraoptimal concentrations of specific peptide in the presence or absence of antigen presenting cells, IL-2, IL-4, and interferon gamma (IFN-gamma) synthesis were comparable to that of activated T cells. The different tolerogenic signals, all capable of inhibiting phase of unresponsiveness. Restimulation of anergic T cells with an antigenic challenge failed to induce lymphokine production, with the exception of allergen-reactive T cells that secreted IFN-gamma. This latter observation is relevant to the desensitization of specific responsiveness in allergic disease.
Publisher: Elsevier BV
Date: 12-2011
Publisher: Wiley
Date: 16-08-2021
DOI: 10.1111/ALL.15036
Abstract: Over the past two decades, precision medicine has advanced diagnostics and treatment of allergic diseases. Component‐resolved analysis of allergen sensitization facilitates stratification of patients. Furthermore, new formulations of allergen immunotherapy (AIT) products can more effectively deliver the relevant components. Molecular insights from the identification of allergen component sensitization and clinical outcomes of treatment with new AIT formulations can now be utilized for a deeper understanding of the nature of the pathogenic immune response in allergy and how this can be corrected by AIT. Fundamental in these processes are the allergen‐specific B and T cells. Within the large B‐ and T‐cell compartments, only those that specifically recognize the allergen with their immunoglobulin (Ig) or T‐cell receptor (TCR), respectively, are of clinical relevance. With peripheral blood allergen‐specific B‐ and T‐cell frequencies below 1%, bulk cell analysis is typically insufficiently sensitive. We here review the latest technologies to detect allergen‐specific B and T cells, as well as new developments in utilizing these tools for diagnostics and therapy monitoring to advance precision medicine for allergic diseases.
Publisher: Wiley
Date: 09-09-2019
DOI: 10.1186/S13601-019-0279-2
Abstract: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. As an ex le for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
Publisher: Wiley
Date: 13-09-2015
DOI: 10.1111/ALL.12686
Abstract: Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
Publisher: Wiley
Date: 12-2002
DOI: 10.1034/J.1398-9995.2002.23699.X
Abstract: Knowledge of dominant T cell epitopes of major allergens recognized by allergic in iduals is required to improve efficacy and safety of allergen immunotherapy. Rye grass pollen (RGP) is the most important source of seasonal aeroallergens in temperate climates and Lol p 1 and Lol p 5 are the two major IgE-reactive allergens. This study aimed to characterize the T cell response to these allergens using a large panel of RGP-sensitive in iduals. Short-term RGP-specific T cell lines (TCL) were generated from 38 RGP-sensitive subjects and stimulated with Lol p 1 and/or Lol p 5 allergens and synthetic 20-mer peptides. Proliferative responses were determined by 3H-thymidine uptake and IL-5 and IFN-gamma in culture supernatants analysed by ELISA. Of 17 subjects tested for reactivity to both allergens 16 (94%) responded to Lol p 1 and/or Lol p 5, establishing these as major T cell-reactive allergens. Sites of T cell reactivity were spread throughout the allergen molecules but regions of high reactivity were found. For Lol p 1 these spanned residues 19-38, 109-128, 154-173, 190-209, and for Lol p 5 37-56, 100-119, 145-164, 154-173, 190-209, 217-236 and 226-245. IL-5 and IFN-gamma were produced by T cells cultured with proliferation-inducing peptides. T cell responses to RGP major allergens have been extensively characterized, providing fundamental information for developing T cell-targeted immunotherapy for RGP allergy.
Publisher: S. Karger AG
Date: 2004
DOI: 10.1159/000079537
Abstract: i Background: /i Hev b 5 is a potent latex allergen. In this study, we characterize the linear B-cell epitopes for three monoclonal antibodies (mAbs) to Hev b 5. i Methods: /i The mAbs included 2 IgG1 (6A10, 3G3) and 1 IgG2b (6F6) isotypes. We used SPOTscan analysis with overlapping octapeptides to identify the binding regions for the antibodies and then methionine substitution analysis to further define the critical amino acids (aa) in each epitope. Site-directed mutagenesis was used to selectively eliminate the IgG binding for each epitope and single and multiple mutations were expressed as recombinant GST fusion proteins. Antibody recognition of the mutant proteins was determined by inhibition ELISA. i Results: /i All three mAbs recognized the same aa sequence by SPOTs analysis with slight variations, and this epitope was repeated 3 times in the Hev b 5 sequence APETEK (63–68), PAEGEK (120–125), and PAEEEK (126–131). Sequential methionine substitution by SPOTsalogue identified K sup /sup , E sup /sup , and K sup /sup as critical aa in each epitope to change by site-directed mutagenesis. Inhibition ELISA with the mutant proteins indicated that epitope 126–131 was the dominant epitope, but mutation of epitope 120–125 was also required to eliminate mAb reactivity to Hev b 5. The antibodies did not appear to recognize the epitope 63–68 in the recombinant fusion protein. i Conclusions: /i We identified an immunodominant B-cell epitope in Hev b 5 that is repeated 3 times within the sequence, making Hev b 5 multivalent. Well-characterized monoclonals recognizing repeated epitopes would be a good choice for immunodetection of Hev b 5 in glove extracts where in idual epitopes could get altered by the manufacturing process.
Publisher: Elsevier BV
Date: 2002
Publisher: Wiley
Date: 03-2004
DOI: 10.1111/J.1365-2222.2004.01900.X
Abstract: IgE is the pivotal-specific effector molecule of allergic reactions yet it remains unclear whether the elevated production of IgE in atopic in iduals is due to superantigen activation of B cell populations, increased antibody class switching to IgE or oligoclonal allergen-driven IgE responses. To increase our understanding of the mechanisms driving IgE responses in allergic disease we examined immunoglobulin variable regions of IgE heavy chain transcripts from three patients with seasonal rhinitis due to grass pollen allergy. Variable domain of heavy chain-epsilon constant domain 1 cDNAs were lified from peripheral blood using a two-step semi-nested PCR, cloned and sequenced. The VH gene family usage in subject A was broadly based, but there were two clusters of sequences using genes VH 3-9 and 3-11 with unusually low levels of somatic mutations, 0-3%. Subject B repeatedly used VH 1-69 and subject C repeatedly used VH 1-02, 1-46 and 5a genes. Most clones were highly mutated being only 86-95% homologous to their germline VH gene counterparts and somatic mutations were more abundant at the complementarity determining rather than framework regions. Multiple sequence alignment revealed both repeated use of particular VH genes as well as clonal relatedness among clusters of IgE transcripts. In contrast to previous studies we observed no preferred VH gene common to IgE transcripts of the three subjects allergic to grass pollen. Moreover, most of the VH gene characteristics of the IgE transcripts were consistent with oligoclonal antigen-driven IgE responses.
Publisher: Wiley
Date: 27-03-2023
DOI: 10.1111/ALL.15719
Abstract: Multidisciplinary systematic assessment improves outcomes in difficult‐to‐treat asthma, but without clear response predictors. Using a treatable‐traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment. We performed latent class analysis using 12 traits on difficult‐to‐treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ‐6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV 1 , exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. Among 241 patients, two airway‐centric profiles were characterized by early‐onset with allergic rhinitis ( n = 46) and adult onset with eosinophilia/chronic rhinosinusitis ( n = 60), respectively, with minimal comorbid or psychosocial traits three non‐airway‐centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance ( n = 51), psychosocial (anxiety, depression, smoking, unemployment) dominance ( n = 72), or multi‐domain impairment ( n = 12). Compared to airway‐centric profiles, non‐airway‐centric profiles had worse baseline ACQ‐6 (2.7 vs. 2.2, p .001) and AQLQ (3.8 vs. 4.5, p .001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway‐centric profiles had more FEV 1 improvement (5.6% vs. 2.2% predicted, p .05) while non‐airway‐centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p = .07) mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p = .782). Distinct trait profiles in difficult‐to‐treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult‐to‐treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.
Publisher: Elsevier BV
Date: 2000
Publisher: Wiley
Date: 20-09-2001
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/IMJ.16_13197
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.JACI.2010.09.027
Abstract: Peanut allergy is a life-threatening condition there is currently no cure. Although whole allergen extracts are used for specific immunotherapy for many allergies, they can cause severe reactions, and even fatalities, in peanut allergy. This study aimed to identify short, T-cell epitope-based peptides that target allergen-specific CD4(+) T cells but do not bind IgE as candidates for safe peanut-specific immunotherapy. Multiple CD4(+) T-cell lines specific for the major peanut allergen Ara h 2 were generated from PBMCs of 16 HLA- erse subjects with peanut allergy by using 5,6-carboxyfluorescein diacetate succinimidylester-based methodology. Proliferation and ELISPOT assays were used to identify dominant epitopes recognized by T-cell lines and to confirm recognition by peripheral blood T cells of epitope-based peptides modified for therapeutic production. HLA restriction of core epitope recognition was investigated by using anti-HLA blocking antibodies and HLA genotyping. Serum-IgE peptide-binding was assessed by dot-blot. Five dominant CD4(+) T-cell epitopes were identified in Ara h 2. In combination, these were presented by HLA-DR, HLA-DP, and HLA-DQ molecules and recognized by T cells from all 16 subjects. Three short peptide variants containing these T-cell epitopes were designed with cysteine-to-serine substitutions to facilitate stability and therapeutic production. Variant peptides showed HLA-binding degeneracy, did not bind peanut-specific serum IgE, and could directly target T(H)2-type T cells in peripheral blood of subjects with allergy. Short CD4(+) T-cell epitope-based Ara h 2 peptides were identified as novel candidates for a T-cell-targeted peanut-specific immunotherapy for an HLA- erse population.
Publisher: Elsevier BV
Date: 05-2000
Abstract: Latex allergy affects health care workers as a high-risk cohort. Hev b 5 is a major latex allergen reacting with serum IgE from 92% of latex-allergic health care workers. Because CD4(+) T-cell recognition is central to the specific immune response to allergens, identification of dominant T-cell epitopes is important for the development of specific immunotherapy for latex allergy. Our purpose was to map T-cell epitopes of Hev b 5 in health care workers. Six latex-allergic health care workers (grade 3 to 4 enzyme allergosorbent test score) were studied. Peripheral blood latex specific 3-week T-cell lines were generated and screened for proliferative response to overlapping 20-mer peptides of Hev b 5. Supernatants collected at 48 hours were analyzed by ELISA for IL-5 and IFN-gamma. Dot immunoblotting with use of recombinant Hev b 5/maltose-binding protein indicated serum-specific IgE in 5 of 6 patients. T-cell reactivity to one or more Hev b 5 peptides was identified in these 5 donors, but not in the sixth. Hev b 5 (46-65) induced T-cell proliferation in all 5 donors. Hev b 5 (109-128) stimulated T cells from 3 of these patients. Proliferative responses were accompanied by substantial IL-5 secretion and minimal IFN-gamma, indicating a T(H)2-predominant cytokine profile. Five of 6 latex-allergic patients demonstrated T-cell responsiveness to Hev b 5 consistent with a major T-cell reactive latex allergen. Two T-cell immunodominant regions of Hev b 5 were identified, and reactivity to these sites was associated with strong IL-5 but minimal IFN-gamma production.
Publisher: Oxford University Press (OUP)
Date: 12-1997
DOI: 10.1086/516995
Publisher: Wiley
Date: 07-2016
DOI: 10.1111/IMJ.13073
Abstract: Atopic eczema, allergic broncho-pulmonary aspergillosis, helminthic infections and rare primary immunodeficiencies are known to elevate total serum immunoglobulin E (IgE) above 1000 IU/mL. However, of 352 patients with IgE >1000 IU/mL seen in our hospital over a 5-year period, less than 50% had these conditions. Markedly elevated IgE levels in the rest of the patients were associated with asthma, allergic rhinitis and food allergy, instances where the test is of limited diagnostic utility.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JAIP.2018.11.037
Abstract: Understanding of dysfunctional breathing in patients with difficult asthma who remain symptomatic despite maximal inhaler therapy is limited. We characterized the pattern of dysfunctional breathing in patients with difficult asthma and identified possible contributory factors. Dysfunctional breathing was identified in patients with difficult asthma using the Nijmegen Questionnaire (score >23). Demographic characteristics, asthma variables, and comorbidities were assessed. Multivariate logistic regression was performed for dysfunctional breathing, adjusted for age, sex, body mass index, and airflow obstruction. Of 157 patients with difficult asthma, 73 (47%) had dysfunctional breathing. Compared with patients without dysfunctional breathing, those with dysfunctional breathing experienced poorer asthma status (symptom control, quality of life, and exacerbation rates) and greater unemployment. In addition, more frequently they had elevated sino-nasal outcome test scores, anxiety, depression, sleep apnea, and gastroesophageal reflux. On multivariate analysis, anxiety (odds ratio [OR], 3.26 95% CI, 1.18-9.01 P = .02), depression (OR, 2.8 95% CI, 1.14-6.9 P = .03), and 22-item sino-nasal outcome test score (OR, 1.03 95% CI, 1.003-1.05 P = .03) were independent risk factors for dysfunctional breathing. Dysfunctional breathing is common in difficult asthma and associated with worse asthma status and unemployment. The independent association with psychological disorders and nasal obstruction highlight an important interaction between comorbid treatable traits in difficult asthma.
Publisher: Wiley
Date: 22-03-2018
DOI: 10.1111/ALL.13406
Abstract: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.
Publisher: Walter de Gruyter GmbH
Date: 1995
DOI: 10.1515/BCHM3.1995.376.5.303
Abstract: Staphylococcal enterotoxin B (SEB) has three essential biological properties that appear to be mediated by particular domains of the protein. As a superantigen, SEB triggers the T cell receptor (TcR) of a selected subset of T cells where the beta chain is encoded by particular V beta gene products. T cell triggering is generally dependent upon the ability of SEB to form a ternary complex with the TcR and MHC class II molecules and this interaction is relatively unrestricted by class II polymorphism. The third property of SEB is its potent toxicity a few nanograms are sufficient to cause vomiting and violent diarrhoea in primates. In this study, we confirm the importance of the amino terminal domain of SEB for stimulation of human T cells. It is clear that the first 138 residues are the minimal mitogenic component of the toxin, and deletion of just seven more residues abrogates all activity. A mutant molecule with an internal deletion of these seven residues (SEB delta 131-138) was mitogenic suggesting that the region can confer stability to the rest of the protein, but does not include contact sites for either class II or the TcR. We further show that the disulphide loop is not essential for T cell recognition and that each of our mutants binds class II molecules with reduced affinity and is subtly variant in the pattern of TcR that it stimulates.
Publisher: Wiley
Date: 03-10-2007
Publisher: Public Library of Science (PLoS)
Date: 28-01-2016
Publisher: Wiley
Date: 09-07-2004
Publisher: Oxford University Press (OUP)
Date: 08-1996
DOI: 10.1046/J.1365-2249.1996.D01-761.X
Abstract: The effects of exposure to HIV-gp120 on proliferation and cytokine production by T cell lines were investigated. T cell lines were generated by stimulation of peripheral blood mononuclear cells from several healthy donors with cross-linked anti-CD3 antibodies and IL-2. These T cell lines exhibited the characteristics of Th1 cells, producing IL-2 and interferon-gamma (IFN-γ), but not IL-4, on stimulation with anti-CD3 antibodies. In the presence of gp120, stimulation with anti-CD3 antibodies was inhibited in terms of both proliferative responses and the secretion of IL-2 and IFN-γ. Similar effects were observed when a T cell line was stimulated in the presence of a synthetic peptide representing the CD4-binding region of gp120. Neither gp120 nor the CD4-binding region peptide had any effect on IL-4 production by the T cell lines. Stimulation through the CD28 pathway partially restored both the proliferative effect and cytokine production by T cell lines in response to anti-CD3 antibodies in the presence of gp120. Anti-CD28 antibodies also partially restored cytokine production when purified CD4+ T cells from a T cell line were stimulated with anti-CD3 antibodies in the presence of gp120. Anti-gp120 antibodies partially or completely reversed the inhibitory effects of gp120 on T cell proliferation. These results indicate that stimulation through the CD28 pathway may restore defective CD4+ T cell responses in HIV-infected in iduals.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JACI.2019.01.053
Abstract: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms (2) nasal, ocular, and asthma symptoms (3) work and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
Publisher: Wiley
Date: 12-1984
DOI: 10.1111/J.1445-5994.1984.TB03789.X
Abstract: The traditional biochemical tests of sympathetic nervous system function used in clinical diagnosis (urine and plasma catecholamine measurements) are indices of "overall" sympathetic nervous activity, and incapable of detecting localised changes in sympathetic tone confined to in idual organs. Recently developed radiotracer methods, which enable the pattern of sympathetic nervous dysfunction in disease states to be delineated, were used to detect abnormalities in regional sympathetic nervous system activity in two patients presenting problems in management. In one, the abnormality of sympathetic function was iatrogenic, a post-sympathectomy denervation of the lower regions of the body, associated with incapacitating postural hypotension. In the other, unexplained persistent sinus tachycardia proved to be due to an increase in sympathetic nervous tone restricted to the innervation of the heart. Knowledge of the underlying sympathetic nervous pathophysiology in these patients influenced the choice of drugs subsequently used in their treatment.
Publisher: Wiley
Date: 11-10-2017
DOI: 10.1111/CEA.13025
Abstract: Visual Analogue Scale (VAS) is a validated tool to assess control in allergic rhinitis patients. The aim of this study was to validate the use of VAS in the MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) app (Allergy Diary) on smartphones screens to evaluate allergic rhinitis symptoms and disease control. Each user filled 4 different VAS measuring overall, nasal, ocular, and asthma symptoms at least once. Following COSMIN guidelines, we evaluated internal consistency, (Cronbach's alpha coefficient and test-retest), reliability (intraclass correlation coefficients), sensitivity, and acceptability of the MASK-Rhinitis VAS. Between 1 August 2015 and 31 July 2016, the app was used 14 612 times in 15 countries. A total of 1225 users used it more than once, during the evaluated period. The tool resulted to be statistically satisfactory, showing excellent internal consistency (Cronbach's test > 0.84, test-retest > 0.7), reliability (>0.9), and acceptability. In addition, the tool had a good sensitivity when users (n = 521) answered the VAS twice in less than 3 hours. The MASK-rhinitis VAS is a reliable and valid tool to assess allergic control on smartphone screens, at the population level.
Publisher: Wiley
Date: 06-2010
Publisher: MDPI AG
Date: 12-02-2021
Abstract: Despite recent technological advances, novel allergenic protein discovery is limited by their low abundance, often due to specific physical characteristics restricting their recovery during the extraction process from various allergen sources. In this study, eight different extraction buffers were compared for their ability to recover proteins from Pacific oyster (Crassostrea gigas). The protein composition was investigated using high resolution mass spectrometry. The antibody IgE-reactivity of each extract was determined using a pool of serum from five shellfish-allergic patients. Most of the investigated buffers showed good capacity to extract proteins from the Pacific oyster. In general, a higher concentration of proteins was recovered using high salt buffers or high pH buffers, subsequently revealing more IgE-reactive bands on immunoblotting. In contrast, low pH buffers resulted in a poor protein recovery and reduced IgE-reactivity. Discovery of additional IgE-reactive proteins in high salt buffers or high pH buffers was associated with an increase in allergen abundance in the extracts. In conclusion, increasing the ionic strength and pH of the buffer improves the solubility of allergenic proteins during the extraction process for oyster tissue. This strategy could also be applied for other difficult-to-extract allergen sources, thereby yielding an improved allergen panel for increased diagnostic efficiency.
Publisher: Wiley
Date: 06-2021
DOI: 10.1111/ALL.14840
Abstract: Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of in iduals are vaccinated. The COVID‐19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide in iduals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and in idual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post‐authorization and post‐marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for in idual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.
Publisher: American Thoracic Society
Date: 15-11-2009
Publisher: Wiley
Date: 04-2004
Publisher: American Society for Microbiology
Date: 09-2010
DOI: 10.1128/CVI.00195-10
Abstract: Scabies, a parasitic skin infestation by the burrowing “itch” mite Sarcoptes scabiei , causes significant health problems for children and adults worldwide. Crusted scabies is a particularly severe form of scabies in which mites multiply into the millions, causing extensive skin crusting. The symptoms and signs of scabies suggest host immunity to the scabies mite, but the specific resistant response in humans remains largely uncharacterized. We used 4 scabies mite recombinant proteins with sequence homology to extensively studied house dust mite allergens to investigate a differential immune response between ordinary scabies and the debilitating crusted form of the disease. Subjects with either disease form showed serum IgE against recombinant S. scabiei cysteine and serine proteases and apolipoprotein, whereas naive subjects showed minimal IgE reactivity. Significantly ( P 0.05) greater serum IgE and IgG4 binding to mite apolipoprotein occurred in subjects with crusted scabies than in those with ordinary scabies. Both subject groups showed strong proliferative responses (peripheral blood mononuclear cells) to the scabies antigens, but the crusted scabies group showed increased secretion of the Th2 cytokines interleukin 5 (IL-5) and IL-13 and decreased Th1 cytokine gamma interferon (IFN-γ) in response to the active cysteine protease. These data confirm that a nonprotective allergic response occurs in the crusted disease form and demonstrate that clinical severity is associated with differences in the type and magnitude of the antibody and cellular responses to scabies proteins. A quantitative IgE inhibition assay identified IgE immunoreactivity of scabies mite antigens distinct from that of house dust mite antigens, which is potentially important for specific scabies diagnosis and therapy.
Publisher: Cold Spring Harbor Laboratory
Date: 18-09-2023
Publisher: American Thoracic Society
Date: 02-1988
Abstract: An association between the use of parenteral corticosteroids in acute asthma and the development of an acute myopathy was first reported in 1977. We report 2 further cases that contribute significantly to our knowledge of this rare complication of the treatment of acute asthma. These cases demonstrate that the acute myopathy is not just a complication of the use of parenteral hydrocortisone in patients requiring ventilatory support during an episode of acute asthma. The acute myopathy can occur with several parenteral corticosteroids, may be severe (with rhabdomyolysis and myoglobinuria), and may have protracted morbidity. Prospective follow-up allowed demonstration of histopathology, electrophysiology, and also the contribution of various pharmacologic agents. Careful analysis of the evidence strongly implicates corticosteroids as the causative agent.
Publisher: Springer US
Date: 1996
Publisher: Public Library of Science (PLoS)
Date: 09-12-2013
Publisher: Wiley
Date: 05-2017
DOI: 10.1111/IMJ.13413
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.MCE.2011.10.009
Abstract: Activin A, a member of the transforming growth factor-β superfamily of cytokines, is a critical controller of inflammation, immunity and fibrosis. It is rapidly released into the blood following a lipopolysaccharide challenge in experimental animals, through activation of the Toll-like receptor 4 signalling pathway. Blocking activin action by pre-treatment with its binding protein, follistatin, modifies the inflammatory cytokine cascade, and reduces the severity of the subsequent inflammatory response and mortality. Likewise, high serum levels of activin A are predictive of death in patients with septicaemia. However, activin A has complex immunomodulatory actions. It is produced by inflammatory macrophages, but can regulate either pro- or anti-inflammatory responses in these cells, depending on their prior activation status. Activin A is also produced by Th2 cells, and stimulates antibody production by B cells and the development of regulatory T cells. Production of activin A during inflammatory responses stimulates fibrosis and tissue remodelling, and follistatin inhibits these actions of activin A. The modulation of activin by follistatin may represent an important therapeutic target for the modulation and amelioration of inflammatory and fibrotic disorders.
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/IMJ.11_13197
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000338290
Abstract: b i Background: /i /b Bahia grass pollen (BaGP) is a major cause of allergic rhinitis. Subcutaneous allergen-specific immunotherapy is effective for grass pollen allergy, but is unsuitable for patients with moderate to severe asthma due to the risk of anaphylaxis. T cell-reactive but IgE nonreactive peptides provide a safer treatment option. This study aimed to identify and characterize dominant CD4 sup + /sup T cell epitope peptides of the major BaGP allergen, Pas n 1. b i Methods: /i /b Pas n 1-specific T cell lines generated from the peripheral blood of BaGP-allergic subjects were tested for proliferative and cytokine response to overlapping 20-mer Pas n 1 peptides. Cross-reactivity to homologous peptides from Lol p 1 and Cyn d 1 of Ryegrass and Bermuda grass pollen, respectively, was assessed using Pas n 1 peptide-specific T cell clones. MHC class II restriction of Pas n 1 peptide T cell recognition was determined by HLA blocking assays and peptide IgE reactivity tested by dot blotting. b i Results: /i /b Three Pas n 1 peptides showed dominant T cell reactivity 15 of 18 (83%) patients responded to one or more of these peptides. T cell clones specific for dominant Pas n 1 peptides showed evidence of species-specific T cell reactivity as well as cross-reactivity with other group 1 grass pollen allergens. The dominant Pas n 1 T cell epitope peptides showed HLA binding ersity and were non-IgE reactive. b i Conclusions: /i /b The immunodominant T cell-reactive Pas n 1 peptides are candidates for safe immunotherapy for in iduals, including those with asthma, who are allergic to Bahia and possibly other grass pollens.
Publisher: Oxford University Press (OUP)
Date: 1990
Abstract: The contribution of the HLA-DRB1, -B3, and -B5 gene products in the recognition of Dermatophagoides spp. (house dust mite) by helper T cells isolated from an atopic in idual (HLA-DRw12, DR7 DRw52b) with perennial rhinitis was investigated. Using a panel of histocompatible and histoincompatible accessory cells, the restriction specificity obtained for a long term T cell suggested that a component of the dust mite reactive repertoire recognized antigen in association with DRB3 gene products. Oligonucleotide DNA typing of the presenting cell panel demonstrated a correlation between the DRw52b allele and T cell responsiveness. Murine fibroblasts expressing DRw52b, but not DRw52a or -c molecules, presented antigen to both the T cell line and cloned T cells (DE26) derived from the line, indicating that the supertypic specificity DRw52b was able to restrict recognition of dust mite antigens. Additional T cell clones (DE9 and DE41) also isolated from the line were restricted by the products of the B1 gene locus (DRw12B1) as determined by murine fibroblasts transfected with the appropriate HLA-DR genes. Clone DE9 was degenerate in its restriction specificity, also recognizing dust mite presented by accessory cells expressing the DR2 subtypes. Presentation by fibroblasts transfected with DRw12B1, DR2Dw2B5 genes and EBV-transformed B cell lines expressing DR2DW21B1 and -B5 indicated that the functional site restricting recognition may be associated with residues 70 and 71 of the DR beta chain helical wall of the antigen combining site. Furthermore, we have recently demonstrated that both T cell clones DE9 and DE26 induce allergen dependent IgE synthesis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 29-07-2016
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.JIM.2014.10.008
Abstract: Food allergies are increasing worldwide, demonstrating a considerable public health concern. Shellfish allergy is one of the major food groups causing allergic sensitization among adults and children, affecting up to 2% of the general world population. Tropomyosin (TM) is the major allergen in shellfish and frequently used in the diagnosis of allergic sensitization and the detection of cross-contaminated food. To improve and establish better and more sensitive diagnostics for allergies and immunotherapeutics, large quantities of pure allergens are required. To establish a reproducible method for the generation of pure recombinant tropomyosin we utilized in this study different Escherichia coli strains (NM522, TOP10 and BL21(DE3)RIPL). In addition, isopropyl-β-D-thiogalactoside (IPTG) induction was compared with a novel auto-induction system to allow the generation of larger quantities of recombinant allergen. We demonstrated that the B-strain of E. coli is better for the expression of TM compared to the K-strain. Moreover, a higher yield could be achieved when using the auto-induction system, with up to 62 mg/l. High yield expressed recombinant TM from King prawn (KP) was compared to recombinant TM from Black tiger prawn (Pen m 1). We demonstrated that recombinant TM from KP and known isoallergen Pen m 1 have very similar molecular and immunological characteristics. Overall, we demonstrate that auto-induction can be used to express larger quantities of recombinant allergens for the development of diagnostic, to quantify allergens as well as immunotherapeutics employing isoallergens.
Publisher: Wiley
Date: 05-05-2021
DOI: 10.1111/ALL.14832
Abstract: Diagnostic tests for allergy rely on detecting allergen‐specific IgE. Component‐resolved diagnostics incorporate multiple defined allergen components to improve the quality of diagnosis and patient care. To develop a new approach for determining sensitization to specific allergen components that utilizes fluorescent protein tetramers for direct staining of IgE on blood basophils by flow cytometry. Recombinant forms of Lol p 1 and Lol p 5 proteins from ryegrass pollen (RGP) and Api m 1 from honeybee venom (BV) were produced, biotinylated, and tetramerized with streptavidin‐fluorochrome conjugates. Blood s les from 50 RGP‐allergic, 41 BV‐allergic, and 26 controls were incubated with fluorescent protein tetramers for flow cytometric evaluation of basophil allergen binding and activation. Allergen tetramers bound to and activated basophils from relevant allergic patients but not controls. Direct fluorescence staining of Api m 1 and Lol p 1 tetramers had greater positive predictive values than basophil activation for BV and RGP allergy, respectively, as defined with receiver operator characteristics (ROC) curves. Staining intensities of allergen tetramers correlated with allergen‐specific IgE levels in serum. Inclusion of multiple allergens coupled with distinct fluorochromes in a single‐tube assay enabled rapid detection of sensitization to both Lol p 1 and Lol p 5 in RGP‐allergic patients and discriminated between controls, BV‐allergic, and RGP‐allergic patients. Our novel flow cytometric assay, termed CytoBas, enables rapid and reliable detection of clinically relevant allergic sensitization. The intensity of fluorescent allergen tetramer staining of basophils has a high positive predictive value for disease, and the assay can be multiplexed for a component‐resolved and differential diagnostic test for allergy.
Publisher: Oxford University Press (OUP)
Date: 1993
Abstract: The induction of non-responsiveness in specific clones of T cells in vivo might be expected to reverse immunologically mediated disease processes. With this goal in mind, experiments in vitro with cloned T cells have investigated the mechanisms of induction of anergy. Resting T cells can be functionally inactivated in vitro by high doses of appropriate peptide in either the presence or absence of antigen presenting cells. During the induction of anergy, the modulation of the surface phenotype of T cells is similar to that of cells proliferating in response to an immunogenic stimulus. The amount of T cell receptor at the cell surface is down regulated, whereas the CD2 and CD25 receptors are increased in density. In contrast, CD28 has been identified as a membrane protein that is differentially regulated during activation and the induction of non-responsiveness. Ligation of CD28 provides an efficient costimulatory signal for activation of T cells. In this report, we show that not only resting cells, but also fully activated T cells can be rendered non-responsive and that this process is accompanied by profound downregulation of CD28, both at the level of cytoplasmic mRNA and surface expression of the mature protein. This observation anticipates clinical intervention in immunologically mediated disease, where the target T cells are more likely to be activated than in a resting state.
Publisher: Wiley
Date: 30-10-2018
DOI: 10.1111/ALL.13628
Abstract: The potential of precision medicine in allergy and asthma has only started to be explored. A significant clarification in the pathophysiology of rhinitis, chronic rhinosinusitis, asthma, food allergy and drug hypersensitivity was made in the last decade. This improved understanding led to a better classification of the distinct phenotypes and to the discovery of new drugs such as biologicals, targeting phenotype-specific mechanisms. Nevertheless, many conditions remain poorly understood such as non-eosinophilic airway diseases or non-IgE-mediated food allergy. Moreover, there is a need to predict the response to specific therapies and the outcome of drug and food provocations. The identification of patients at risk of progression towards severity is also an unmet need in order to establish adequate preventive or therapeutic measures. The implementation of precision medicine in the clinical practice requires the identification of phenotype-specific markers measurable in biological matrices. To become useful, these biomarkers need to be quantifiable by reliable systems, and in s les obtained in an easy, rapid and cost-efficient way. In the last years, significant research resources have been put in the identification of valid biomarkers for asthma and allergic diseases. This review summarizes these recent advances with focus on the biomarkers with higher clinical applicability.
Publisher: Wiley
Date: 30-09-2021
DOI: 10.1111/ALL.14838
Abstract: Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID‐19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID‐19 vaccines due to high risk of death. In very rare instances, the COVID‐19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA‐EAACI‐EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID‐19 vaccines. Anaphylaxis to COVID‐19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
Publisher: Wiley
Date: 20-03-2004
DOI: 10.1111/J.1365-2044.2005.04529.X
Abstract: The plasma expander Gelofusine (succinylated gelatin) is a recognised cause of peri-operative anaphylaxis. Current diagnosis of Gelofusine sensitivity is by skin testing, a procedure that itself carries a risk of allergic reaction. We evaluated the reliability of the in vitro basophil activation test as a diagnostic assay for Gelofusine sensitivity in subjects with a clinical history highly suggestive of Gelofusine allergy. Six patients with peri-operative anaphylaxis clinically attributed to Gelofusine were skin tested to confirm sensitivity. Control subjects included three healthy subjects and five subjects allergic to a neuromuscular blocking drug, all negative on Gelofusine skin testing. Whole blood basophil activation to Gelofusine was analysed by flow cytometry for CD63 surface expression. All of the Gelofusine sensitive patients and one of the control allergic subjects showed positive basophil activation to Gelofusine. In this series of subjects, the basophil activation test for Gelofusine allergy had a sensitivity of 100% and a specificity of 87.5%. Our findings suggest that basophil activation testing is a safe and reliable in vitro assay for prediction or confirmation of Gelofusine sensitivity in patients with high clinical suspicion of Gelofusine-induced anaphylaxis.
Publisher: Elsevier BV
Date: 07-1993
DOI: 10.1016/0091-6749(93)90044-G
Abstract: IgE antibodies reactive with the group II allergens of Dermatophagoides species (house dust mite [HDM]) are a major component of the allergic immune response in HDM-allergic atopic in iduals. Here we demonstrate, with the use of overlapping synthetic peptides of the group II allergen of Dermatophagoides pteronyssinus (Der p II), that polyclonal T cells isolated from the majority of atopic HDM-allergic in iduals and healthy nonatopic control subjects respond to Der p II and that T-cell epitopes are present in all regions of the protein. From comparison of peptide-specific T-cell proliferation in both groups of in iduals, it appears that together peptides 61-86 and 78-104 are the most frequently recognized (16 of 18 in iduals). We also observed that nine of the 18 in iduals responded to T-cell epitopes in the region 11-50, and with Der p II-reactive T-cell clones, three distinct T-cell epitopes were mapped within the sequence 11-35. Also, with the use of T-cell clones, two additional epitopes were identified at residues 81-96 and 91-101. These results suggest that T-cell epitopes located in these regions (11-50 and 61-104) are immunodominant. The value of this information in the potential application of Der p II peptides to desensitize HDM allergic responses is discussed.
Publisher: Elsevier BV
Date: 1988
Publisher: Wiley
Date: 04-11-2011
DOI: 10.1111/J.1398-9995.2011.02728.X
Abstract: This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.
Publisher: Elsevier BV
Date: 03-2007
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.RMED.2017.10.012
Abstract: The Melbourne thunderstorm asthma epidemic in November 2016 was unprecedented in scale and impact. We systematically reviewed our hospital's patients with thunderstorm asthma to identify key risk factors. Of 85 adult patients assessed, the majority (60%) had no prior diagnosis of asthma. However, allergic rhinitis during the grass pollen season was almost universal (99%), as were ryegrass pollen sensitization (100%) and exposure to the outdoor environment during the thunderstorm (94%). Airborne pollen levels on the thunderstorm day were extreme. We conclude that ryegrass pollen sensitization, clinical allergic rhinitis, and acute allergen exposure constitute a risk-factor 'trifecta' for thunderstorm asthma.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Wiley
Date: 16-05-2015
DOI: 10.1111/CEA.12554
Publisher: Frontiers Media SA
Date: 14-05-2018
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JACI.2019.01.032
Abstract: The Agency for Healthcare Research and Quality and the National Institute of Allergy and Infectious Diseases organized a workshop to develop trial concepts that could improve the use and effectiveness of aeroallergen immunotherapy (AAIT). Expert groups were formed to accomplish the following tasks: (1) propose a study design to compare the effectiveness and safety of subcutaneous versus sublingual AAIT (2) propose a study design to compare the effectiveness and safety of AAIT by using 1 or a few allergens versus all or most allergens to which a patient is sensitized (3) propose a study design to determine whether AAIT can alter the progression of childhood allergic airways disease and (4) propose a study design to determine the optimal dose and duration of AAIT to achieve maximal effectiveness with acceptable safety. Study designs were presented by the workgroups, extensively discussed at the workshop, and revised for this report. The proposed trials would be of long duration and require large highly characterized patient populations. Scientific caveats and feasibility matters are discussed. These concepts are intended to help the development of clinical trials that can address some of the major questions related to the practice of AAIT for the management and prevention of allergic airways disease.
Publisher: Wiley
Date: 19-11-2015
DOI: 10.1111/CEA.12671
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JAIP.2019.02.042
Abstract: Severe asthma is complex and heterogeneous ad hoc outpatient assessment can be suboptimal. Systematic evaluation improves outcomes and is recommended by international guidelines. Electronic templates improve physician performance and clinical processes, and may be useful in severe asthma systematic evaluation. We developed the Severe Asthma Global Evaluation (SAGE) electronic platform to streamline this process, via Research Electronic Data Capture (REDCap). It incorporates: a questionnaire battery for patient completion before clinical consultation asthma and comorbidity modules a clinical summary page in an asthma management module a nurse educator module a structured panel discussion record and an automatically generated report incorporating all key data. SAGE incorporates 282 clinician input fields, with a typical consultation requiring completion of 169. To streamline the process SAGE contains 34 autocalculations and 20 decision support tools. It incorporates all 95 core variables of the International Severe Asthma Registry, with which it is directly compatible. SAGE improves symptom control and exacerbations in patients with difficult asthma. In conclusion, we developed and validated an electronic platform that facilitates a comprehensive but streamlined systematic evaluation of severe asthma that is available for free download via REDCap. Its use enhances management of patients with severe asthma and facilitates audit and international research collaboration.
Publisher: Wiley
Date: 09-06-2017
DOI: 10.1111/ALL.13177
Abstract: Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global 50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.
Publisher: Informa UK Limited
Date: 12-2022
DOI: 10.2147/JAA.S390125
Publisher: Wiley
Date: 04-06-2019
DOI: 10.1111/ALL.13851
Abstract: The specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules. This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring of allergic diseases, asthma, allergic and nonallergic rhinitis, and new approaches to the diagnosis and treatment of drug hypersensitivity reactions are discussed in further detail. In the third section, unmet needs and future research areas for the treatment of allergic diseases are highlighted with topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen‐specific immunotherapy for airway disease. Unknowns and future research needs are discussed at the end of each subsection.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Wiley
Date: 22-11-2019
DOI: 10.1111/ALL.13611
Publisher: Public Library of Science (PLoS)
Date: 19-06-2013
Publisher: Elsevier BV
Date: 11-1994
DOI: 10.1016/0091-6749(94)90152-X
Abstract: Recent analysis of the usage of T-cell receptor (TcR) beta chain variable region (V beta) gene elements by house dust mite (HDM)-reactive T cells from an atopic donor suggested that TcR-V beta 3 gene products may form a major component of the human T-cell repertoire reactive to this common allergen. In this study a peptide analog of the TcR-V beta 3 complementarity determining region 2 (CDR2) is shown to inhibit the polyclonal human T-cell response to HDM this effect is specific because inhibition is dependent on the presence of V beta 3 + T cells. This experimental approach has been used to determine whether the pattern seen in T-cell clones derived from one atopic donor reflects TcR-V beta usage in the polyclonal response to allergen in the general population. Inhibition of more than 50% of the polyclonal response to allergen by V beta 3-CDR2 peptide was observed in 16 of 21 donors tested, suggesting that TcR-V beta 3 gene usage may form a major component of the human HDM repertoire and as such offer a suitable target for T cell-directed specific immunotherapy in HDM-allergic in iduals. Depletion of CD8+ T cells abolishes peptide-mediated inhibition of CD4+ T-cell proliferation to HDM, suggesting that induction of a CD8+ regulatory T-cell subset by the CDR2 peptide may modulate HDM-specific allergic T-cell responses.
Publisher: Wiley
Date: 24-07-2001
DOI: 10.1016/S0014-5793(01)02661-8
Abstract: The aim of this study was to investigate the molecular basis of human IgE-allergen interaction by screening a phage-displayed peptide library with an allergen-specific human IgE-mimicking monoclonal antibody (mAb). A mAb that reacted with major grass pollen allergens was successfully identified and shown to inhibit human IgE-allergen interaction. Biopanning of a phage-displayed random peptide library with this mAb yielded a 12 amino acid long mimotope. A synthetic peptide based on this 12-mer mimotope inhibited mAb and human IgE binding to grass pollen extracts. Our results indicate that such synthetic peptide mimotopes of allergens have potential as novel therapeutic agents.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.JACI.2016.11.043
Abstract: Synthetic peptide immunoregulatory epitopes are a new class of immunotherapy to treat allergic rhinoconjunctivitis (ARC). Grass allergen peptides, comprising 7 synthetic T-cell epitopes derived from Cyn d 1, Lol p 5, Dac g 5, Hol l 5, and Phl p 5, is investigated for treatment of grass pollen-induced ARC. We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides. A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen-induced allergy (18-65 years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6 nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12 nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12 nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed. Two hundred eighty-two subjects were randomized. Significantly greater improvement (reduction of total rhinoconjunctivitis symptom score from baseline to PTC) occurred across days 2 to 4 with grass allergen peptide 8x6Q2W versus placebo (-5.4 vs -3.8, respectively P = .0346). Greater improvement at PTC also occurred for grass allergen peptide 8x6Q2W versus placebo (P = .0403) in patients with more symptomatic ARC. No safety signals were detected. Grass allergen peptide 8x6Q2W significantly improved ARC symptoms after rye grass allergen challenge in an EEU with an acceptable safety profile.
Publisher: Elsevier BV
Date: 04-1999
DOI: 10.1016/0091-6749(86)90362-3
Abstract: The plasma membrane contains discrete nanometer-sized domains that are resistant to non-ionic detergents, and which are called detergent resistant membrane domains (DRMDs) or lipid rafts. Exposure of host cells to pathogenic bacteria has been shown to induce the re-distribution of specific host proteins between DRMDs and detergent soluble membranes, which leads to the initiation of cell signaling that enable pathogens to access host cells. DRMDs have been shown to play a role in the invasion of Brucella into host macrophages and the formation of replicative phagosomes called Brucella-containing vacuoles (BCVs). In this study we sought to characterize changes to the protein expression profiles in DRMDs and to respective cellular pathways and networks of Mono Mac 6 cells in response to the adherence of rough VTRM1 and smooth 16 M B. melitensis strains. DRMDs were extracted from Mono Mac 6 cells exposed for 2 minutes at 4°C to Brucella (no infection occurs) and from unexposed control cells. Protein expression was determined using the non-gel based quantitative iTRAQ (Isobaric Tags for Relative and Absolute Quantitation) mass spectrometry technique. Using the identified iTRAQ proteins we performed enrichment analyses and probed constructed human biochemical networks for interactions and metabolic reactions. We identified 149 proteins, which either became enriched, depleted or whose amounts did not change in DRMDs upon Brucella exposure. Several of these proteins were distinctly enriched or depleted in DRMDs upon exposure to rough and smooth B. melitensis strains which results in the differential engagement of cellular pathways and networks immediately upon Brucella encounter. For some of the proteins such as myosin 9, small G protein signaling modulator 3, lysine-specific demethylase 5D, erlin-2, and voltage-dependent anion-selective channel protein 2, we observed extreme differential depletion or enrichment in DRMDs. The identified proteins and pathways could provide the basis for novel ways of treating or diagnosing Brucellosis.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JAIP.2016.12.030
Abstract: Systematic evaluation is advocated for difficult asthma, but how best to deliver such care is unclear and outcome data are scarce. We describe our institution's structured approach to difficult asthma management and report on the outcomes of such an approach. Eighty-two consecutive patients with difficult asthma referred to our clinic from respiratory specialists were evaluated in 3 key areas: diagnostic confirmation, comorbidity detection, and inflammatory phenotyping. We then optimized treatment including relevant comorbidity interventions. The outpatient protocol was supported by comorbidity questionnaires, an electronic clinic template, and standardized panel discussion. Asthma outcomes were assessed at 6 months. Sixty-eight patients completed follow-up. Asthma diagnosis was refuted in 3 patients and the remaining 65 patients were included in the study analysis. There was no overall escalation of inhaled or oral corticosteroids. Patients had a median of 3 comorbidities, and a median of 3 comorbidity interventions. Control of chronic rhinosinusitis and dysfunctional breathing improved among patients with these diagnoses (22-item Sino-Nasal Outcome Test score from 47 ± 20 to 37 ± 22, P = .017 Nijmegen score from 32 ± 6 to 25 ± 9, P = .003). There were overall improvements in the Asthma Control Test score (from 14 ± 5 to 16 ± 6, P < .001), the Asthma Quality of Life Questionnaire (from 4.29 ± 1.4 to 4.65 ± 1.5, P = .073), and the frequency of exacerbations over 6 months (from 2 [interquartile range, 0-4] to 0 [interquartile range, 0-2], P < .001). In patients referred with difficult asthma from respiratory specialists, a structured approach coupled with targeted comorbidity interventions improved control of key comorbidities and enhanced asthma outcomes.
Publisher: Wiley
Date: 11-10-2019
DOI: 10.1111/ALL.13609
Publisher: Elsevier BV
Date: 10-2017
Publisher: Wiley
Date: 30-11-1999
DOI: 10.1016/S0014-5793(99)01576-8
Abstract: A novel isoform of a major rye grass pollen allergen Lol p 5 was isolated from a cDNA expression library. The new isoform, Lol p 5C, shares 95% amino acid sequence identity with Lol p 5A. Both isoforms demonstrated shared antigenic activity but different allergenic activities. Recombinant Lol p 5C demonstrated 100% IgE reactivity in 22 rye grass pollen sensitive patients. In comparison, recombinant Lol p 5A showed IgE reactivity in less than 64% of the patients. Therefore, Lol p 5C represents a novel and highly IgE-reactive isoform allergen of rye grass pollen.
Publisher: Proceedings of the National Academy of Sciences
Date: 11-1990
Abstract: The exotoxins produced by certain strains of Staphylococcus aureus are able to stimulate powerful polyclonal proliferative responses and to induce nonresponsiveness by clonal deletion of T lymphocytes expressing the appropriate T-cell antigen receptor V beta gene products. This paper examines the ability of S. aureus enterotoxins to modulate the responsiveness of human CD4+ T lymphocytes with defined antigen specificity. It was observed that certain S. aureus toxins were able to activate and induce anergy in hemagglutinin-reactive T cells expressing V beta 3+ elements. After exposure to S. aureus enterotoxins A, B, and D in the absence of antigen-presenting cells, the T cells failed to respond to their natural ligand presented in an immunogenic form, despite enhanced proliferation to exogenous interleukin 2. The S. aureus toxin-induced anergy was associated with modulation of T-cell membrane receptors down-regulation of the T-cell antigen receptor was concomitant with enhanced expression of CD2 and CD25. Interestingly, CD28 was increased only on stimulation, suggesting this protein may be differentially expressed by activated and anergic T cells. These results indicate that bacterial toxins are able to induce antigen-specific nonresponsiveness in human T cells, the application of which may be relevant in the regulation of T cells expressing a particular family of V beta gene products.
Publisher: Elsevier BV
Date: 02-2015
Publisher: Wiley
Date: 26-10-2004
DOI: 10.1111/J.1398-9995.2004.00584.X
Abstract: Clinically effective allergen-specific immunotherapy correlates with decreased circulating allergen-specific IL-4+ T cells but increased IFN-gamma+ cells at sites of allergen challenge. Whether immunotherapy promotes trafficking of IFN-gamma+ T cells to peripheral tissues is unknown. As aeroallergen is administered at higher concentrations during immunotherapy than those encountered naturally, the effect of allergen concentration on adhesion molecule (CD62L and CD49d) and chemokine receptor (CCR3 and CCR5) expression by peripheral-blood T cells was analysed in parallel with cytokine production. House dust mite-allergic donor peripheral blood mononuclear cells were cultured for 14 days with different allergen concentrations. Cytokine profiles of were analysed by flow cytometry. Cultures stimulated with 100 microg/ml house dust mite extract compared with 1 microg/ml had increased proportions and numbers of CD62Llo, CD49dhi or CCR5+ T cells expressing IFN-gamma. CCR3-positive CD4+ and CD8+ T cell numbers were very low and did not differ between cultures. In contrast the proportions of 'peripheral tissue trafficking' CD4+ T cells expressing IL-4 were decreased in cultures stimulated with high in comparison with low allergen concentration. These results indicate the importance of achieving high allergen doses during immunotherapy to promote IFN-gamma production and expression of a 'peripheral tissue trafficking' phenotype by allergen-specific CD4+ and CD8+ T cells. The net change in cytokine milieu at sites of allergen encounter would then down-regulate clinical manifestations of allergic disease.
Publisher: The American Association of Immunologists
Date: 02-2012
Abstract: Nanoparticles are being developed for erse biomedical applications, but there is concern about their potential to promote inflammation, particularly in the lung. Although a variety of ambient, anthropogenic and man-made nanoparticles can promote lung inflammation, little is known about the long-term immunomodulatory effects of inert noninflammatory nanoparticles. We previously showed polystyrene 50-nm nanoparticles coated with the neutral amino acid glycine (PS50G nanoparticles) are not inflammatory and are taken up preferentially by dendritic cells (DCs) in the periphery. We tested the effects of such nanoparticles on pulmonary DC function and the development of acute allergic airway inflammation. Surprisingly, exposure to PS50G nanoparticles did not exacerbate but instead inhibited key features of allergic airway inflammation including lung airway and parenchymal inflammation, airway epithelial mucus production, and serum allergen-specific IgE and allergen-specific Th2 cytokines in the lung-draining lymph node (LN) after allergen challenge 1 mo later. PS50G nanoparticles themselves did not induce lung oxidative stress or cardiac or lung inflammation. Mechanistically, PS50G nanoparticles did not impair peripheral allergen sensitization but exerted their effect at the lung allergen challenge phase by inhibiting expansion of CD11c+MHCIIhi DCs in the lung and draining LN and allergen-laden CD11bhiMHCIIhi DCs in the lung after allergen challenge. PS50G nanoparticles further suppressed the ability of CD11bhi DCs in the draining LN of allergen-challenged mice to induce proliferation of OVA-specific CD4+ T cells. The discovery that a defined type of nanoparticle can inhibit, rather than promote, lung inflammation via modulation of DC function opens the door to the discovery of other nanoparticle types with exciting beneficial properties.
Publisher: Wiley
Date: 08-2002
DOI: 10.1046/J.1365-2745.2002.01432.X
Abstract: Although allergy to latex is a well-characterized phenomenon, some hospitals continue to provide staff with powdered latex gloves as an option to low- or non-powdered gloves. We aimed to measure the extent to which inhalation of latex particles could be reduced by the use of protective masks or by replacing powdered latex gloves with non-powdered latex gloves. Twenty healthcare workers in a hospital setting wore nasal air s lers (NAS) and Institute of Occupational Medicine (IOM) s lers for four 20-min periods. Subjects wore powdered gloves, non-powdered gloves and no gloves during three s ling periods, and in the fourth, subjects applied an aerosol barrier face-mask or a particulate face-mask (N95) while wearing powdered gloves. All s les were stained for particles bearing Hev b 5 allergen by the Halogen assay. All subjects inhaled Hev b 5 bearing particles in all s ling periods. IOM s lers collected particles at 70% of the rate of NAS. The number of particles inhaled while wearing powdered gloves was 23.8-fold higher than when not wearing gloves and 9.7-fold higher than when wearing non-powdered latex gloves (P < 0.0001). Wearing an aerosol barrier mask did not significantly reduce the number of particles inhaled (P = 0.108), while use of particulate masks significantly reduced the number of particles inhaled by 17.4-fold (P = 0.003). Use of non-powdered gloves is the most effective method of reducing occupational aeroallergen exposure to latex arising from gloves. However, secondary protection using particulate masks is a valid alternative, and may be helpful for preventing respiratory sensitization.
Publisher: Wiley
Date: 09-1995
DOI: 10.1111/J.1365-2222.1995.TB00026.X
Abstract: It has been reported for the peripheral T cell repertoire that CD4 molecules may enhance adhesion between T cells and antigen presenting cells and, through their physical association with T cell antigen receptors, contribute to signal transduction. The aims of this study were to determine if the modulation of CD4 molecules had differential effects on T cell recognition, antigen induced cytokine (IL-4 and IFN gamma), release and the induction of specific anergy for human TH-0, Th-1 and TH-2 cells. A panel of anti-CD4 antibodies was examined for its ability to modulate T cell proliferation, cytokine production and tolerance induction in house dust mite (TH-0 and TH-2) and influenza haemagglutinin (TH-1) specific human CD4+ T cell clones all restricted by DRB1*1101 and isolated from dust mite allergic in iduals. We observed that anti-CD4 antibodies may inhibit or enhance antigen mediated T cell proliferation, which may reflect the differential requirements of T cells for selective functions of CD4. Furthermore, IFN gamma and IL-4 production was differentially modulated depending on the specificity of the anti-CD4 antibody and the clone of T cells. However, pretreatment of T cells with anti-CD4 antibody alone neither induced nor enhanced the susceptibility of T cells to peptide mediated anergy. Antigen recognition by different subsets of human CD4+ T cells has differential requirements on CD4, whereas the induction of specific anergy appeared to be independent of the functions of CD4 molecules. Antigen induced IFN gamma production was more susceptible than IL-4 to the inhibitory effects of anti-CD4 antibodies. Furthermore, it appeared that certain anti-CD4 antibodies can dissociate antigen induced IFN gamma and IL-4 production, and may downregulate IFN gamma synthesis without inhibiting antigen dependent proliferation.
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.MOLIMM.2008.08.267
Abstract: Bahia grass, Paspalum notatum, is a clinically important subtropical grass with a prolonged pollination season from spring to autumn. We aimed to clone and characterise the major Bahia grass pollen allergen, Pas n 1. Grass pollen-allergic patients presenting to a tertiary hospital allergy clinic were tested for IgE reactivity with Bahia grass pollen extract by skin prick testing, ImmunoCAP, ELISA and immunoblotting. Using primers deduced from the N-terminal peptide sequence of a group 1 allergen of Bahia grass pollen extract separated by two-dimensional gel electrophoresis, the complete Pas n 1 cDNA was obtained by rapid lification of cDNA ends and cloned. Biological relevance of recombinant Pas n 1 expressed in Escherichia coli was assessed by serum IgE reactivity and basophil activation. Twenty-nine of 34 (85%) consecutive patients presenting with grass pollen allergy were skin prick test positive to Bahia grass pollen. The Pas n 1 cDNA has sequence homology with the beta-expansin 1 glycoprotein family and is more closely related to the maize pollen group 1 allergen (85% identity) than to ryegrass Lol p 1 or Timothy grass Phl p 1 (64 and 66% identity, respectively). rPas n 1 reacted with serum IgE in 47 of 55 (85%) Bahia grass pollen-allergic patients, activated basophils and inhibited serum IgE reactivity with the 29 kDa band of Bahia grass pollen extract. In conclusion the cDNA for the major group 1 allergen of the subtropical Bahia grass pollen, Pas n 1, was identified and cloned. rPas n 1 is immunologically active and is a valuable reagent for diagnosis and specific immunotherapy of grass pollen allergy.
Publisher: Wiley
Date: 04-2020
DOI: 10.1111/ALL.14134
Abstract: Since the introduction of allergen immunotherapy (AIT) over 100 years ago, focus has been on standardization of allergen extracts, with reliable molecular composition of allergens receiving the highest attention. While adjuvants play a major role in European AIT, they have been less well studied. In this Position Paper, we summarize current unmet needs of adjuvants in AIT citing current evidence. Four adjuvants are used in products marketed in Europe: aluminium hydroxide (Al(OH)
Publisher: Wiley
Date: 06-10-2022
DOI: 10.1111/ALL.15107
Abstract: IgG2 responses are associated with repeated antigen exposure and display highly mutated variable domains. A recent study highlighted a role of IgG2+ memory B cells and allergen-specific IgG2 levels after a 3rd consecutive pre-seasonal sublingual allergen immunotherapy (AIT) with grass pollen tablet. Herein, we aim to explore changes in allergen-specific IgG2 in in iduals undergoing house dust mite immunotherapy (HDM-AIT) and explore whether the interrelationship with other humoral responses (i.e., IgG4 and IgE) may discriminate between high and low responders. Levels of serum Dermatophagoides pteronyssinus and Dermatophagoides farinae-specific IgG2, IgG4, and IgE antibodies were measured by ELISA or ImmunoCap in a sub-group of in iduals enrolled in a randomized, double-blind, placebo-controlled, sublingual AIT study evaluating the safety and efficacy of a 300 IR HDM tablet. After 1-year sublingual AIT, HDM-specific serum IgG2 responses increase mostly in high versus low responders and are distinctive according to the clinical benefit. Higher correlation between HDM-specific IgG2, IgE, and/or IgG4 responses is seen in subjects benefiting the most from HDM-AIT as indicated by changes in Average Total Combined Scores. More strikingly, statistically significant correlation between HDM-specific IgG2 and IgE responses is only observed in in iduals stratified as high responders. We provide evidence for coordinated serum immune responses upon AIT in HDM-allergic subjects exhibiting high clinical benefit when compared with low responders. Assessing HDM-specific IgE, IgG2, and IgG4 in serum could be used as follow-up combined markers to support decision as to AIT continuation and/or adaptation.
Publisher: Elsevier BV
Date: 10-1991
DOI: 10.1016/0198-8859(91)90107-K
Abstract: The relative contributions of putative T-cell receptor (TCR)-contacting and peptide-binding residues of a major histocompatibility complex (MHC) class II restriction element to serologic and antigen-specific T-cell recognition were investigated by site-specific mutagenesis. Amino acids 70 and 71 in the DR beta 1 domain of DR4 Dw10 are uniquely differnet from the other Dw subtypes of DR4. Residue 70 is predicted to be located at the membrane-distal surface of the class II molecule, where it may influence T-cell recognition by a direct interaction with a TCR. Residue 71 is predicted to form part of the antigen-binding groove where its influence on T-cell recognition may be mediated indirectly via an effect on peptide binding. Transfected murine L cells were produced expressing the products of DR4 Dw10B genes in which the codons for residues 70 and 71 had been mutated towards DR4 Dw14. Support for the predicted orientations of beta-chain residues 70 and 71 was lent by the observation that only residue 70 plays an important role in the formation of a serologic determinant. Mutation of this residue was sufficient to produce recovery of recognition by a human monoclonal antibody, NI, which has specificity for all the DR4 subtypes with the exception of DR4 Dw10. The human T-cell clone HA1.7, specific for influenza virus hemagglutinin (HA) peptide 307-319 and restricted by DR1 Dw1, exhibits degeneracy of MHC restriction on the DR4 Dw subtypes with the exception of DR4 Dw10.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 10-2016
Publisher: Elsevier BV
Date: 11-1992
DOI: 10.1016/0091-6749(92)90098-M
Abstract: The activation of CD4+ T lymphocytes, which play a central role in allergic inflammation, depends on the recognition of allergen-derived peptides in association with major histocompatibility complex class II gene products. In this report we demonstrate, at a clonal level, that a component of the T-cell repertoire reactive with Dermatophagoides spp. (house dust mite) in atopic in iduals, is restricted by HLA-DP class II molecules. This supports the recent results emerging from genetic epidemiologic studies that indicate positive associations between the HLA-DP phenotype and immune responsiveness to a variety of common allergens. Our findings also reveal that the T cells restricted by HLA-DP recognize a species-specific epitope located in the group I allergen of Dermatophagoides pteronyssinus (residues 101-119). Furthermore, we report that the pretreatment of the T cells restricted by HLA-DP with the Der p I peptide renders them nonresponsive to an immunogenic challenge with house dust mite allergen, and the loss of antigen-dependent proliferation is associated with downregulation of membrane expression of the T-cell antigen receptor. The ability to functionally inactivate T cells restricted by HLA-DP, as well as those that recognize allergen in association with HLA-DR class II molecules, suggests that desensitization with allergen-derived peptides may have therapeutic potential in the management of allergic diseases irrespective of their HLA class II association.
Publisher: Wiley
Date: 14-05-2021
DOI: 10.1111/ALL.14815
Abstract: Although there are many asymptomatic patients, one of the problems of COVID‐19 is early recognition of the disease. COVID‐19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID‐19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA‐EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. A modified Delphi process was used. The ARIA members who were seeing COVID‐19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID‐19, common cold and allergic rhinitis. Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two‐way ANOVA revealed significant differences in the symptom intensity between the three diseases ( p .001). This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID‐19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
Publisher: Elsevier BV
Date: 02-1996
DOI: 10.1016/S0091-6749(96)70318-4
Abstract: Overdose prevention for people who use illicit drugs is essential during the current overdose crisis. Peer support is a process whereby in iduals with lived or living experience of a particular phenomenon provide support to others by explicitly drawing on these experiences. This review provides a systematic search and evidence synthesis of peer support within overdose prevention interventions for people who use illicit drugs. A systematic search of six databases (CINAHL, SocINDEX, PsycINFO, MEDLINE, Scopus, and Web of Knowledge) was conducted in November 2020 for papers published in English between 2000 and 2020. Following screening and full-text review, 46 papers met criteria and were included in this review. A thematic analysis approach was used to synthesize themes. Important findings include: the value of peers in creating trusted services the ersity of peers' roles the implications of barriers on peer-involved overdose prevention interventions and the stress and trauma experienced by peers. Peers play a pivotal role in overdose prevention interventions for people who use illicit drugs and are essential to the acceptability and feasibility of such services. However, peers face considerable challenges within their roles, including trauma and burnout. Future interventions must consider how to support and strengthen peer roles in overdose settings.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.MOLIMM.2010.12.013
Abstract: Bahia grass, Paspalum notatum, is an important pollen allergen source with a long season of pollination and wide distribution in subtropical and temperate regions. We aimed to characterize the 55 kDa allergen of Bahia grass pollen (BaGP) and ascertain its clinical importance. BaGP extract was separated by 2D-PAGE and immunoblotted with serum IgE of a grass pollen-allergic patient. The amino-terminal protein sequence of the predominant allergen isoform at 55 kDa had similarity with the group 13 allergens of Timothy grass and maize pollen, Phl p 13 and Zea m 13. Four sequences obtained by rapid lification of the allergen cDNA ends represented multiple isoforms of Pas n 13. The predicted full length cDNA for Pas n 13 encoded a 423 amino acid glycoprotein including a signal peptide of 28 residues and with a predicted pI of 7.0. Tandem mass spectrometry of tryptic peptides of 2D gel spots identified peptides specific to the deduced amino acid sequence for each of the four Pas n 13 cDNA, representing 47% of the predicted mature protein sequence of Pas n 13. There was 80.6% and 72.6% amino acid identity with Zea m 13 and Phl p 13, respectively. Reactivity with a Phl p 13-specific monoclonal antibody AF6 supported designation of this allergen as Pas n 13. The allergen was purified from BaGP extract by ammonium sulphate precipitation, hydrophobic interaction and size exclusion chromatography. Purified Pas n 13 reacted with serum IgE of 34 of 71 (48%) grass pollen-allergic patients and specifically inhibited IgE reactivity with the 55 kDa band of BaGP for two grass pollen-allergic donors. Four isoforms of Pas n 13 from pI 6.3-7.8 had IgE-reactivity with grass pollen allergic sera. The allergenic activity of purified Pas n 13 was demonstrated by activation of basophils from whole blood of three grass pollen-allergic donors tested but not control donors. Pas n 13 is thus a clinically relevant pollen allergen of the subtropical Bahia grass likely to be important in eliciting seasonal allergic rhinitis and asthma in grass pollen-allergic patients.
Publisher: S. Karger AG
Date: 1989
DOI: 10.1159/000234775
Abstract: A panel of human CD4 sup + /sup T cell clones specific for the house dust mite was isolated from an atopic in idual with perennial rhinitis. Soluble antigen specificity was defined using proliferation assays and subsequently the antigenic determinants recognized by some of these clones were mapped using nitrocellulose immunoblots of fractionated i Dermatophagoides /i spp. Both cross-reactive and species-specific T cell clones were identified and in some instances their specificity could be mapped to the serologically defined i Der f /i l, i Der p /i I and i Der f /i II allergens. In comparison, the serum antibody response showed additional specificity for i Der f /i lll. The antigen recognition by six of these clones was found to be restricted by HLA-DR gene products.
Publisher: American Chemical Society (ACS)
Date: 29-12-2008
DOI: 10.1021/JF073330C
Abstract: Regulations introduced by the Food Standards Australia New Zealand in December 2002 require all wine and wine product labels in Australia to identify the presence of a processing aid, additive or other ingredient, which is known to be a potential allergen. The objective of this study was to establish sensitive assays to detect and measure allergenic proteins from commonly used processing aids in final bottled wine. Sensitive and specific enzyme-linked immunosorbent assays (ELISA) were developed and established for the proteins casein, ovalbumin, and peanut. Lower limits of detection of these proteins were 8, 1, and 8 ng/mL, respectively. A panel of 153 commercially available bottled Australian wines were tested by these ELISA, and except for two red wines known to contain added whole eggs, residuals of these food allergens were not detected in any wine. These findings are consistent with a lack of residual potentially allergenic egg-, milk-, or nut-derived processing aids in final bottled wine produced in Australia according to good manufacturing practice at a concentration that could cause an adverse reaction in egg, milk, or peanut/tree-nut allergic adult consumers.
Publisher: Rockefeller University Press
Date: 06-1992
Abstract: The Staphylococcal enterotoxin superantigens stimulate vigorous responses in T cells bearing certain T cell antigen receptor (TCR) V beta regions. In addition to activation, these superantigens also impart negative signals to T cells resulting in a profound state of unresponsiveness or anergy. The Staphylococcus aureus enterotoxins (SE) B and C2 bind to a closely related site on major histocompatibility complex (MHC) human leukocyte antigen (HLA)-DR1 molecules. Only SEB, however, interacts with the TCR V beta 3 region of HA1.7, a human HLA-DR1 restricted T cell clone specific for influenza haemagglutinin. In competition experiments, we demonstrated that the induction of anergy in HA1.7 by SEB is unaffected by the presence of SEC2. These results suggest that SEB-induced anergy is MHC independent and involves a direct interaction between the TCR and SEB. To resolve definitively whether SEB binds directly to T cells in the absence of MHC class II molecules, the cDNAs encoding the HA1.7 TCR were transfected into an MHC class II-negative human T cell line. The addition of SEB to these transfectants resulted in the downregulation of cell surface TCR expression, an increase in the concentration of intracellular calcium ions, the production of lymphokines, and reduced responsiveness to a subsequent challenge with SEB. We conclude that SEB interacts directly with the TCR in the absence of cointeraction with MHC class II molecules, and that this interaction may induce anergy in HA1.7.
Publisher: The Endocrine Society
Date: 09-2013
DOI: 10.1210/JC.2012-4050
Abstract: A 42-year-old woman presented with a rapidly enlarging right-sided thyroid mass and underwent hemithyroidectomy. Riedel's thyroiditis was only diagnosed upon surgical decompression of the right carotid artery 2 years later. She became more symptomatic as Riedel's thyroiditis progressed, and mediastinal fibrosclerosis developed over the next 12 months. Oral prednisolone failed to improve her condition, and she was commenced on tamoxifen. Despite initial improvement, her symptoms recurred 2 years later, mainly arising from compression of the trachea and esophagus at the thoracic inlet. Fluorodeoxyglucose positron emission tomographic scan showed locally advanced active invasive fibrosclerosis in the neck and mediastinum. An elevated activin-A level of 218 pg/mL was consistent with active inflammation. IgG subtypes (including IgG4) were normal. Two courses of iv methylprednisolone were given but only produced transient improvement. Subsequently, the patient received 3 doses of i.v. rituximab at monthly intervals and had prompt sustained symptomatic improvement. Activin-A level decreased to 122 pg/mL 10 months after rituximab therapy. Fluorodeoxyglucose positron emission tomographic scan 6 weeks after therapy showed reduction in inflammation. A further scan at 10 months demonstrated ongoing response to rituximab. This is a case of refractory Riedel's thyroiditis with symptomatic, biochemical, and radiological improvement that has persisted 14 months after rituximab. The likelihood and duration of response to rituximab in Riedel's thyroiditis requires further study.
Publisher: Wiley
Date: 04-2004
Publisher: The American Association of Immunologists
Date: 11-2004
DOI: 10.4049/JIMMUNOL.173.9.5872
Abstract: Hev b 6.01 is a major allergen of natural rubber latex with sensitization of 70–86% of latex glove-allergic subjects. Recently, we mapped the immunodominant T cell sites of Hev b 6.01 to the highly IgE-reactive hevein (Hev b 6.02) domain. Hev b 6.01 contains 14 cysteine residues with multiple disulphide bridges stabilizing tertiary conformation. With the goal of a standardized specific immunotherapy we developed hypoallergenic Hev b 6.01 mutants by site-directed mutagenesis of selected cysteine residues (3, 12, 17, and 41) within the Hev b 6.02 domain. Peptides corresponding to the Hev b 6.02 domain of two of the mutants were also synthesized. These mutants and peptide variants showed markedly decreased or ablated latex-allergic patient serum IgE binding by immunoblotting and ELISA. Basophil activation testing confirmed markedly decreased activation with successive cysteine substitutions of the mutants and complete abrogation with the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide. Retention of T cell reactivity is crucial for effective specific immunotherapy and all mutants and peptide variants maintained their latex-specific T cell reactivity. The ablated allergenicity but retained T cell reactivity of the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide suggests this peptide is a suitable candidate for inclusion in a latex immunotherapy preparation.
Publisher: Elsevier BV
Date: 03-2013
Publisher: Public Library of Science (PLoS)
Date: 08-03-2017
Publisher: MDPI AG
Date: 17-12-2021
DOI: 10.3390/JOF7121088
Abstract: Armillaria species have a global distribution and play various roles in the natural ecosystems, e.g., pathogens, decomposers, and mycorrhizal associates. However, their taxonomic boundaries, speciation processes, and origin are poorly understood. Here, we used a phylogenetic approach with 358 s lings from Europe, East Asia, and North America to delimit the species boundaries and to discern the evolutionary forces underpinning ergence and evolution. Three species delimitation methods indicated multiple unrecognized phylogenetic species, and biological species recognition did not reflect the natural evolutionary relationships within Armillaria for instance, biological species of A. mellea and D. tabescens are ergent and cryptic species/lineages exist associated with their geographic distributions in Europe, North America, and East Asia. While the species-rich and ergent Gallica superclade might represent three phylogenetic species (PS I, PS II, and A. nabsnona) that undergo speciation. The PS II contained four lineages with cryptic ersity associated with the geographic distribution. The genus Armillaria likely originated from East Asia around 21.8 Mya in early Miocene when Boreotropical flora (56–33.9 Mya) and the Bering land bridge might have facilitated transcontinental dispersal of Armillaria species. The Gallica superclade arose at 9.1 Mya and the concurrent vicariance events of Bering Strait opening and the uplift of the northern Tibetan plateau might be important factors in driving the lineage ergence.
Publisher: Wiley
Date: 21-05-2017
DOI: 10.1111/ALL.13162
Abstract: Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for in iduals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.JACI.2013.01.054
Abstract: Exacerbations of asthma are thought to be caused by airflow obstruction resulting from airway inflammation, bronchospasm, and mucus plugging. Histologic evidence suggests the small airways, including acinar air spaces, are involved however, this has not been corroborated in vivo by measurements of peripheral small-airway function. We sought to determine whether asthma severity is linked to small-airway function, particularly in patients with acute severe asthma. Eighteen subjects admitted for an asthma exacerbation underwent lung function testing, including measures of acinar ventilation heterogeneity (S(acin)) and conductive ventilation heterogeneity (S(cond)) using the multiple-breath nitrogen washout. Treatment requirement was defined according to Global Initiative for Asthma scores. Data were compared with those obtained in 19 patients with stable asthma. For the asthma exacerbation group, the median FEV1 was 59% of predicted value (95% CI, 45% to 75% of predicted value), the median S(cond) value was 185% of predicted value (95% CI, 119% to 245% of predicted value), and the median S(acin) value was 225% of predicted value (95% CI, 143% to 392% of predicted value). FEV1 (percent predicted) was correlated with S(acin) (percent predicted) values (Spearman rho = -0.67, P = .006) but not with S(cond) (percent predicted) values (P > .1). The Global Initiative for Asthma score was significantly related to S(acin) (percent predicted) (Spearman rho = 0.59, P = .016) but not to S(cond) (percent predicted) values (P > .1). The unstable group was characterized by considerably lower forced vital capacity (P < .001) and higher S(cond) (P = .001) values than the unstable group. In a subgroup of 11 unstable patients who could be reviewed after 4 weeks, FEV1, forced vital capacity, S(acin), and S(cond) values showed marked improvements. Our findings suggest that unstable asthma is characterized by a combined abnormality in the acinar and conductive lung zones, both of which are partly reversible. Functional abnormality in the acinar lung zone in particular showed a direct correlation with airflow obstruction and treatment requirement in patients with acute severe asthma.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2012
Publisher: Future Medicine Ltd
Date: 09-1997
DOI: 10.2217/IMT.10.47
Abstract: Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. Chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing, as well as variable airflow obstruction within the lung. With time, such airflow obstruction may become permanent due to remodeling. It has been treated for more than 100 years by subcutaneous immunotherapy with allergen extracts but in recent years, other forms and types of immunotherapy have been introduced. Perhaps the most successful of these to date, is sublingual immunotherapy, which has attained significant usage in European countries but has yet to make inroads into clinical practice in North America. Other mechanisms to modify the inflammatory responses of asthma have included immunotherapy with recombinant allergens, the use of allergen peptides targeting antigen-specific T cells and the administration of Toll-like receptor agonists coupled to allergen proteins. As the inflammatory responses in asthma frequently involve IgE, a modified monoclonal antibody to IgE and interfering with its binding to the IgE receptor have gained acceptance for treating severe allergic asthma. Other monoclonal antibodies or recombinant receptor antagonists are being assessed for their ability to block other contributors to the inflammatory response. Finally, attempts have been made to generate autoantibody responses to cytokines implicated in asthma. Most of these therapies aim to modify or inhibit the so-called Th 2 immune response, which is implicated in many forms of asthma, or to inhibit cytokines involved in these responses. However, an added benefit of classical immunotherapy seems to be the ability to prevent the allergic progression to new sensitivities and new forms of allergic disease.
Publisher: Elsevier BV
Date: 02-1997
DOI: 10.1016/S0091-6749(97)70111-8
Abstract: Variable selection in finite mixture of regression (FMR) models is frequently used in statistical modeling. The majority of applications of variable selection in FMR models use a normal distribution for regression error. Such assumptions are unsuitable for a set of data containing a group or groups of observations with asymmetric behavior. In this paper, we introduce a variable selection procedure for FMR models using the skew-normal distribution. With appropriate choice of the tuning parameters, we establish the theoretical properties of our procedure, including consistency in variable selection and the oracle property in estimation. To estimate the parameters of the model, a modified EM algorithm for numerical computations is developed. The methodology is illustrated through numerical experiments and a real data ex le.
Publisher: Informa UK Limited
Date: 15-06-2022
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1199
Publisher: Annual Reviews
Date: 04-1991
DOI: 10.1146/ANNUREV.IY.09.040191.000435
Abstract: CD4+ T lymphocytes initiate and regulate both the specific and nonspecific effector mechanisms of allergic immune responses. The definition of immunogenic components within allergens has allowed the specificity of the T-cell repertoire to be examined, and the refinement of their molecular structure is now facilitating the mapping of functional epitopes. Nevertheless, the immunological mechanisms that distinguish between atopic and nonatopic states remain unclear as knowledge of the complex network of cytokines in the regulation of immune responses unfolds, this problem may be resolved. Population genetics indicates that susceptibility to allergic disease is partly determined by products of the major histocompatibility gene complex. The use of molecular genetic probes and monoclonal T cells demonstrates the functional importance of both the HLA-DRAB1 and -DRAB3 gene products in T-cell recognition of allergen. Collectively, this information has made it possible to develop in vitro models examining the modulation of responsiveness to allergens.
Publisher: Elsevier BV
Date: 05-1988
DOI: 10.1016/0022-1759(88)90076-2
Abstract: Antigen insolubilised on nitrocellulose is able to activate T lymphocytes following presentation by appropriate accessory cells. Furthermore, complex mixtures of antigens can be fractionated by polyacrylamide gel electrophoresis under denaturing conditions (SDS-PAGE), transferred to nitrocellulose membranes and then added to T cell proliferation assays. This allows a direct screening for recognition of in idual polypeptides by monoclonal and polyclonal T cell populations, without a requirement for extensive biochemical purification and in the absence of initial serological preselection of antigen. The potential use of this technique for screening of recombinant DNA libraries for expression of antigens recognised by T cells is also illustrated. The technical aspects of T cell recognition of solid-phase antigen and its application to the identification of immunodominant epitopes with the potential to modulate T cell-mediated immunity is reviewed.
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.JAIP.2019.12.037
Abstract: Guidelines endorse systematic assessment for severe asthma, with data indicating benefit across multiple outcome domains. We examined which patients respond to systematic assessment and whether oral corticosteroid burden can be decreased independent of monoclonal biologic use. Specialist-referred patients are assessed systematically for difficult asthma at our center. We undertook a responder analysis for improvements in the domains of symptom control, quality of life, exacerbations, and airflow obstruction, assessed 6 months after initial assessment. Multivariate analyses were performed for each domain to identify predictors of response. Changes in oral corticosteroid burden were also measured, stratified by monoclonal biologics commenced during assessment. Among 161 patients assessed systematically, 64% had a reduction in exacerbations, 54% achieved minimum clinically important differences for both symptom control and quality of life, and 40% increased their forced expiratory volume in 1 second by ≥100 mL. Altogether, 87% of patients with asthma improved in at least 1 domain. The most consistent predictor of response across domains was poorer baseline asthma status. There was a substantial reduction in mean chronic oral corticosteroid dose (11-5 mg, n = 46, P < .001), even after excluding 7 patients commenced on monoclonal biologics (11-5.6 mg, n = 39, P < .001). Almost 90% of patients undergoing systematic assessment for difficult asthma improve significantly in at least 1 key asthma outcome, with few reliable predictors of response. The halving of oral corticosteroid burden during systematic assessment is independent of, and comparable in magnitude with, that achieved by monoclonal biologics.
Publisher: Informa Healthcare
Date: 03-2000
Abstract: Allergic in iduals respond to an environmental allergen encounter by producing T-cell cytokines, predominantly IL-4 and IL-5, which in turn drive the production of allergen-specific IgE antibodies and recruitment of an eosinophil-rich inflammatory infiltrate. Allergen-specific immunotherapy (SIT) involves the repeated injection of the allergen to specifically downregulate this predominantly Th2-type immune response. SIT is a clinically proven effective treatment for allergic diseases, including rhinoconjunctivitis and asthma. However, despite having been in clinical practice since early this century, its use remains empirical. Best practice protocols are based on clinical experience and include recommendations for selecting patients for treatment, SIT regimes and avoidance of adverse events. More rational and safer SIT regimes will result from new insights into the underlying immune mechanisms for allergic disease, in particular the critical role of helper T-cells in orchestrating this response. The development of recombinant techniques for producing purified allergens and allergen derivatives has led to a dramatic improvement in the ability to standardise allergen preparations and to develop novel vaccines for allergy treatment. Potential vaccines include short peptides based on dominant T-cell epitopes of allergens, allergen fragments and mutant allergens. All of these preparations are designed to target T-cells without binding IgE and inducing local and systemic side effects. Additional strategies under consideration include DNA vaccines and fusion protein constructs incorporating immunomodulatory elements such as bacterial cell proteins, cytokines and immunostimulatory sequences of DNA. Different forms of allergens are being evaluated for the more practical mucosal administration of allergy vaccines. The identification of recombinant allergens suitable for diagnostic use and the development of reliable laboratory assays, based on T-cell function to monitor clinical efficacy of SIT, are important practical outcomes from this research.
Publisher: Wiley
Date: 09-2003
Publisher: S. Karger AG
Date: 2002
DOI: 10.1159/000053868
Abstract: i Background: /i Bermuda grass pollen (BGP) is an increasingly important seasonal aeroallergen in Australia and other subtropical and temperate regions. BGP shares minimal allergenic cross-reactivity with pollens of rye grass or other Pooideae grasses often used for desensitization regimens in grass pollen allergy. Current allergen immunotherapy is seldom used in asthmatic patients due to IgE-mediated side effects. Since clinically effective immunotherapy is linked with altered allergen-specific T cell response, characterisation of human T cell reactivity to Cyn d 1, the major B cell allergen of BGP, should permit the design of effective and safe immunotherapy for BGP allergy. i Methods: /i Short-term BGP-specific CD4+ T cell lines were established from peripheral blood of 14 BGP-sensitive patients before and after conventional 50% BGP and 50% 7-grass mix subcutaneous specific allergen immunotherapy (SIT). T cell ersity of antigen specificity and function was assessed by proliferation and cytokine production to BGP, Cyn d 1 and Cyn d 1 peptides. i Results: /i Three highly immunogenic regions of Cyn d 1 were identified in 13/14 patients pre-SIT: Cyn d 1 (109–128), (181–209) and (217–241). The SIT regimen was clinically efficacious. Following SIT, decreased proliferation to BGP, Cyn d 1 and Cyn d 1 peptides was observed with a marked decrease in the IL-5:IFN-γ ratio. i Conclusions: /i Cyn d 1 is a major T cell allergen of BGP. Decreased Cyn d 1-specific IL-5 dominant T cell responses were observed in association with clinically effective treatment with the 50% BGP and 50% 7-grass mix. Identified dominant T cell regions of Cyn d 1 should facilitate safer vaccine development for BGP-induced asthma in addition to rhinitis.
Publisher: Wiley
Date: 18-01-2013
Abstract: Microbial contamination of grass pollens could affect sensitization, subsequent allergic response, and efficacy of allergen-specific immunotherapy. We investigated whether bacterial immunomodulatory substances can direct PBMC responses of allergic and nonatopic subjects against ryegrass pollen (RGP) toward Th1, Th2, or regulatory T (Treg) cells. Aqueous extracts of RGP with high or low LPS were fractionated into large and small molecular weight (MW) components by diafiltration. CFSE-labeled PBMCs from allergic and nonatopic subjects were stimulated with RGP extracts (RGPEs) and analyzed for cytokine secretion and T-cell responses. High LPS RGPE increased IFN-γ(+) Th1 and IL-4(+) Th2 effector cell induction and consistently decreased CD4(+) Foxp3(hi) Treg-cell induction. IL-10-producing T-cell frequency was unaltered, but IL-10 secretion was increased by high LPS RGPE. RGPE-stimulation of TLR-transfected cell lines revealed that high LPS pollen also contained a TLR2-ligand, and both batches a TLR9-ligand. Beta-1,3-glucans were detected in large and small MW fractions and were also T-cell stimulatory. In conclusion, coexposure to allergen and proinflammatory microbial stimuli does not convert an established Th2- into a Th1-response. Instead, proinflammatory responses are exacerbated and Foxp3(hi) Treg-cell induction is decreased. These findings show that adjuvants for specific immunotherapy should enhance Treg cells rather than target immune deviation from Th2 to Th1.
Publisher: Wiley
Date: 22-05-2008
DOI: 10.1111/J.1365-2222.2008.02984.X
Abstract: Allergy to natural rubber latex products emerged as an important clinical condition following an increase in the use of latex gloves for barrier protection in the early 1980s. In addition to latex glove users, other high-risk groups with different latex exposure include spina bifida patients and others with multiple surgical procedures. Subjects with fruit and vegetable allergy are also at risk due to cross-reactive allergens. Following the significant advances in the identification and characterization of common aeroallergens, latex allergy was well placed to become an excellent model of therapy. Awareness of latex allergy and modes of sensitization enabled epidemiological studies to inform allergen avoidance initiatives, substantially reducing inadvertent exposure in major hospitals in Western countries. Spina bifida is often identified in utero or soon after birth, allowing vigorous latex allergen avoidance with enhanced efficacy of primary prevention. However, changing demographics of latex allergy and technological revolution in countries such as China and India are predicted to unleash a second wave of latex allergy reemphasizing the incentive for improved manufacturing procedures for latex products. The desirable high tensile strength and elasticity of natural rubber latex have made the commercial identification of good alternatives very difficult but this would also be attractive for primary prevention. In addition, an effective specific immunotherapy regimen would be valuable for selected high-risk atopic in iduals. Current subcutaneous and sublingual immunotherapy schedules have been tested for treatment of latex allergy with evidence of efficacy but the risks of adverse events are high. For such potent allergens as latex, hypoallergenic but T cell-reactive preparations are required for clinical use. Identification of allergenic components of latex products, with generation of monoclonal antibodies and recombinant allergens, allowed sequence determination and mapping of T cell and B cell epitopes. Together, these reagents and data facilitated improved diagnostics and investigation of novel-specific therapeutics. Potential hypoallergenic latex preparations identified include modified non-IgE-reactive allergen molecules and short T cell epitope peptides. The co-administration of adjunct therapies such as anti-IgE or corticosteroids and of appropriate adjuvants for induction of regulatory T cell response offers promise for clinically effective, safe latex-specific vaccines.
Publisher: Wiley
Date: 1996
DOI: 10.1111/J.1365-2222.1996.TB00052.X
Abstract: Selected cytokines produced by allergen specific CD4+ T cells from atopic in iduals contribute to both the specific and non-specific effector mechanisms of the allergic immune response. The chemokine family of cytokines and tumour necrosis factor (TNF)-alpha are leucocyte regulatory and proinflammatory molecules. The chemokines include interleukin (IL)-8 and the RANTES/SIS cytokines. There has been no systematic survey of chemokine production in T-cell subtypes. Because of their wide range of biological properties, it might be expected that they would be closely regulated by T cells. This paper illustrates one way (through the characterization of T-cell clones) these questions might be addressed. Northern blot analysis was used to quantitate steady state transcription of selected cytokine genes and enzyme linked immunosorbent assay (ELISA) was used to quantitate soluble product. mRNA expression of the chemokines (IL-8, HuMIP-1 alpha and HuMIP-1 beta) and TNF alpha is upregulated in TH2-like cloned house dust mite reactive human CD4+ T cells under conditions of activation and during the induction phase of anergy. Although the development of anergy superinduces mRNA for both IL-8 and TNF alpha, protein production is low compared with that released during activation. In contrast, RANTES, a chemoattractant for CD4+/CD45RO+ memory T cells, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and anergy induction. The production of IL-2, IL-4 and IL-5 mRNA and proteins during the induction of anergy peaks at 2 h after stimulation, whereas the kinetics following activation of the T cells is delayed in comparison. These data show that the induction of the anergic state coincides with post-transcriptional regulation of selected cytokine genes. Further study of these phenomena will impact on our understanding of the mechanisms of induction of anergy and the regulation of allergic immune responses in desensitization.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2010
Publisher: Elsevier BV
Date: 2002
Publisher: Wiley
Date: 02-11-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2019
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.JAIP.2014.12.008
Abstract: Allergic bronchopulmonary aspergillosis (ABPA) often presents with persistently uncontrolled asthma despite the use of corticosteroids and antifungal therapy. Omalizumab is a humanized anti-IgE monoclonal antibody currently used to treat severe asthma. The aim was to assess the clinical and immunologic effects of omalizumab in ABPA in a randomized, placebo-controlled trial. Patients with chronic ABPA were randomized to 4-month treatment with omalizumab (750 mg monthly) or placebo followed by a 3-month washout period in a cross-over design. The main endpoint was number of exacerbations. Other clinical endpoints included lung function, exhaled nitric oxide (FeNO), quality of life and symptoms. In vitro basophil activation to Aspergillus fumigatus extract and basophil FcεR1 and surface-bound IgE levels were assessed by flow cytometry. Thirteen patients were recruited with mean total IgE 2314 ± 2125 IU/mL. Exacerbations occurred less frequently during the active treatment phase compared with the placebo period (2 vs 12 events, P = .048). Mean FeNO decreased from 30.5 to 17.1 ppb during omalizumab treatment (P = .03). Basophil sensitivity to A. fumigatus and surface-bound IgE and FcεR1 levels decreased significantly after omalizumab but not after placebo. Omalizumab can be used safely to treat ABPA, despite high serum IgE levels. Clinical improvement was accompanied by decreased basophil reactivity to A. fumigatus and FcεR1 and surface-bound IgE levels.
Publisher: Wiley
Date: 09-03-2023
DOI: 10.1111/ALL.15685
Publisher: Wiley
Date: 12-2016
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.JACI.2017.03.050
Abstract: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. We sought to provide a targeted update of the ARIA guidelines. The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.
Publisher: Wiley
Date: 04-2002
DOI: 10.1046/J.0954-7894.2002.01355.X
Abstract: Hev b 5 is a major latex allergen recognized predominantly by latex-allergic health care workers (HCWs). Recombinant Hev b 5 (rHev b 5) was previously expressed as a fusion protein with maltose binding protein (MBP), itself an immunogenic molecule therefore non-fusion rHev b 5 is desirable. Moreover, standardized immunological assays for the detection of Hev b 5 are currently lacking and may have important implications for both allergen avoidance and diagnosis in latex allergy. To generate and use Hev b 5-specific mAbs to determine the relative abundance of Hev b 5 in different latex extracts, correlating this with the IgE reactivity of latex-allergic HCWs and to produce non-fusion rHev b 5. For the production of mAbs, mice were immunized with rHev b 5/MBP fusion protein and mAbs selected with rHev b 5/MBP but not MBP reactivity. The mAb reactivity was compared with polyclonal IgE from latex-allergic HCWs using direct and inhibition ELISA and immunoblot assays. Recombinant Hev b 5 was expressed and purified in the pPROEX-HTa bacterial expression system. Four Hev b 5-specific mAbs were produced. Immunoblotting and ELISA using the mAbs indicate abundant Hev b 5 in high protein powdered latex glove extracts as compared with crude latex sap extracts. High quality surgical gloves with no detectable protein have no detectable Hev b 5. Inhibition ELISAs using serum IgE from latex-allergic HCWs and Hev b 5-specific mAbs gave strong correlation. Non-fusion recombinant Hev b 5 was successfully expressed and purified, showing reactivity with both the Hev b 5-specific mAbs and serum IgE of latex-allergic HCWs. Hev b 5-specific mAbs and human IgE from latex-allergic HCWs demonstrate the greater content of Hev b 5 in high protein powdered glove extracts. This may explain the observed higher frequency of sensitization to this allergen in HCWs.
Publisher: Wiley
Date: 30-04-2019
DOI: 10.1111/ALL.13701
Abstract: Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.ANAI.2016.04.024
Abstract: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in asthma is often made in patients with total serum IgE levels greater than 1,000 IU/mL in conjunction with evidence of Aspergillus sensitization. The specificity of total serum IgE for the diagnosis of ABPA is low even when combined with serum Aspergillus specific IgE. To determine the prevalence of ABPA and to identify alternative clinical predictors for ABPA among asthmatic patients with a total serum IgE level greater than 1,000 IU/ml. This study was conducted in a tertiary hospital in Melbourne, Australia, with a large asthma and allergy service. Patients with asthma and total serum IgE levels greater than 1,000 IU/ml from January 1, 2005, through December 31, 2014, were included. Patients were considered to have concomitant allergic conditions if they had atopic eczema, allergic rhinitis, or both. The diagnosis of ABPA was based on the managing physician's documented diagnosis and referenced to criteria proposed by the International Society for Human and Fungal Mycology. The prevalence of ABPA in our cohort was 15.8%. Older age, elevated total serum IgE level, reduced lung function, and the absence of other concomitant allergic conditions increased the risk of ABPA. After multivariate logistic regression, patients without concomitant allergic conditions had an odds ratio of 4.4 (95% confidence interval, 1.9-10.1 P = .001) for ABPA when compared with patients with allergic conditions. The absence of atopic eczema and allergic rhinitis in these patients increases the likelihood of ABPA. Eliciting an accurate allergy history may be a useful bedside clinical tool when considering the diagnosis of ABPA.
Publisher: Wiley
Date: 12-2009
Publisher: Elsevier BV
Date: 1988
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.JACI.2015.04.047
Abstract: Allergen immunotherapy (AIT) has been used to treat allergic disease since the early 1900s. Despite numerous clinical trials and meta-analyses proving AIT efficacious, it remains underused and is estimated to be used in less than 10% of patients with allergic rhinitis or asthma worldwide. In addition, there are large differences between regions, which are not only due to socioeconomic status. There is practically no controversy about the use of AIT in the treatment of allergic rhinitis and allergic asthma, but for atopic dermatitis or food allergy, the indications for AIT are not well defined. The elaboration of a wider consensus is of utmost importance because AIT is the only treatment that can change the course of allergic disease by preventing the development of asthma and new allergen sensitizations and by inducing allergen-specific immune tolerance. Safer and more effective AIT strategies are being continuously developed both through elaboration of new allergen preparations and adjuvants and alternate routes of administration. A number of guidelines, consensus documents, or both are available on both the international and national levels. The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice. Consequently, the International Collaboration in Asthma, Allergy and Immunology, formed by the European Academy of Allergy and Clinical Immunology the American Academy of Allergy, Asthma & Immunology the American College of Allergy, Asthma & Immunology and the World Allergy Organization, has decided to issue an international consensus on AIT.
Strongyloides infection as a reversible cause of chronic urticaria
Publisher: Informa UK Limited
Date: 02-2019
DOI: 10.2147/JAA.S167292
Publisher: Elsevier BV
Date: 06-2000
Abstract: Phage display is an advanced technology that can be used to characterize the interactions of antibody with antigen at the molecular level. It provides valuable data when applied to the investigation of IgE interaction with allergens. The aim of this rostrum article is to provide an explanation of the potential of phage display for increasing the understanding of allergen-IgE interaction, the discovery of diagnostic reagents, and the development of novel therapeutics for the treatment of allergic disease. The significance of initial studies that have applied phage display technology in allergy research will be highlighted. Phage display has been used to clone human IgE to timothy grass pollen allergen Phl p 5, to characterize the epitopes for murine and human antibodies to a birch pollen allergen Bet v 1, and to elucidate the epitopes of a murine mAb to the house dust mite allergen Der p 1. The technology has identified peptides that functionally mimic sites of human IgE constant domains and that were used to raise antiserum for blocking binding of IgE to the FcepsilonRI on basophils and subsequent release of histamine. Phage display has also been used to characterize novel peanut and fungal allergens. The method has been used to increase our understanding of the molecular basis of allergen-IgE interactions and to develop clinically relevant reagents with the pharmacologic potential to block the effector phase of allergic reactions. Many advances from these early studies are likely as phage display technology evolves and allergists gain expertise in its research applications.
Publisher: American Thoracic Society
Date: 03-2000
Publisher: Elsevier BV
Date: 05-1992
DOI: 10.1016/0091-6749(92)90228-T
Abstract: To assess the impact of adoption of a national health program on homeless care in the United States, care for this group in Britain's National Health Service (NHS) was evaluated. Although hospital and medication charges are eliminated, primary care for the homeless lacks central government directive, suffers from overlap of statutory agencies and mechanistic biases, is disproportionately delivered in emergency rooms, and has relied on advocacy by the non-profit sector. Disadvantages of this void in NHS provision are marginalization of the homeless and continuation of a two-class care system. Removal of financial barriers to care by enactment of a national health program in the US would not solve all issues related to delivery of quality care for the homeless unless its structure addressed the special needs of disenfranchised groups.
Publisher: Cambridge University Press (CUP)
Date: 2007
DOI: 10.1017/S1462399407000208
Abstract: Peanut ( Arachis hypogaea ) allergy is a major cause of food-induced anaphylaxis, with increasing prevalence worldwide. To date, there is no cure for peanut allergy, and, unlike many other food allergies, it usually persists through to adulthood. Prevention of exposure to peanuts is managed through strict avoidance, which can be compromised by the frequent use of peanuts and peanut products in food preparations. Conventional subcutaneous-injection allergen immunotherapy using crude peanut extract is not a recommended treatment because of the risk of severe side effects, largely as a result of specific IgE antibodies. Consequently, there is an urgent need to develop a suitable peanut allergen preparation that can induce specific clinical and immunological tolerance to peanuts in allergic in iduals without adverse side effects. This requires detailed molecular and immunological characterisation of the allergenic components of peanut. This article reviews current knowledge on clinically relevant peanut allergens, in particular Ara h 1, Ara h 2 and Ara h 3, together with options for T-cell-reactive but non-IgE-binding allergen variants for specific immunotherapeutic strategies. These include T-cell-epitope peptide and hypoallergenic mutant vaccines. Alternative routes of administration such as sublingual are also considered, and appropriate adjuvants for delivering effective treatments at these sites examined.
Publisher: Wiley
Date: 06-2001
DOI: 10.1002/1522-2683(200106)22:10<1900::AID-ELPS1900>3.0.CO;2-4
Publisher: Elsevier BV
Date: 07-1993
DOI: 10.1016/0091-6749(93)90042-E
Abstract: Neuropeptide Y (NPY) and neutral endopeptidase have been shown to regulate the response of airway smooth muscle. However, their interactions have not been studied. To determine the role of NPY and endogenous neutral endopeptidase in regulating the effects of NPY, we investigated the effects of NPY and a neutral endopeptidase inhibitor, phosphoramidon, on the contractile response of isolated human bronchial segments to electrical field stimulation (EFS). Concentrations of up to 10(-6) mol/L of NPY did not change resting tension. NPY inhibited the cholinergic contractions induced by EFS at 5 Hz dose-dependently. Phosphoramidon (10(-5) mol/L) enhanced the inhibitory effect of NPY on EFS-induced contractions at 5 Hz. NPY (3 x 10(-7) mol/L) shifted the frequency-response curve for EFS (1 to 50 Hz) to the right and significantly increased the mean logarithm of frequency that produced 50% of maximal contraction (control: 0.54 +/- 0.07 versus NPY: 0.79 +/- 0.09, p < 0.05). Phosphoramidon (10(-5) mol/L) did not affect the frequency response to EFS, but enhanced the inhibitory effect of NPY (3 x 10(-7) mol/L) on frequency response to EFS, resulting in a significant increase in the mean logarithm of frequency that produced 50% of maximal contraction (NPY: 0.79 +/- 0.09 versus NPY plus phosphoramidon: 1.18 +/- 0.15, p < 0.05). NPY (3 x 10(-7) mol/L) did not affect the response of tissues to exogenously applied acetylcholine. These observations suggest that NPY inhibits the output of acetylcholine from nerve endings and that endogenous neutral endopeptidase modulates the effect of NPY in the human airway by inactivating this peptide.
Publisher: Informa UK Limited
Date: 25-11-2014
DOI: 10.3109/03602532.2013.859688
Abstract: Engineered nanoparticles (ENP), which could be composed of inorganic metals, metal oxides, metalloids, organic biodegradable and inorganic biocompatible polymers, are being used as carriers for vaccine and drug delivery. There is also increasing interest in their application as delivery agents for the treatment of a variety of lung diseases. Although many studies have shown ENP can be effectively and safely used to enhance the delivery of drugs and vaccines in the periphery, there is concern that some ENP could promote inflammation, with unknown consequences for lung immune homeostasis. In this study, we review research on the effects of ENP on lung immunity, focusing on recent studies using erse animal models of human lung disease. We summarize how the inflammatory and immune response to ENP is influenced by the erse biophysical and chemical characteristics of the particles including composition, size and mode of delivery. We further discuss newly described unexpected beneficial properties of ENP administered into the lung, where biocompatible polystyrene or silver nanoparticles can by themselves decrease susceptibility to allergic airways inflammation. Increasing our understanding of the differential effects of erse types of nanoparticles on pulmonary immune homeostasis, particularly previously underappreciated beneficial outcomes, supports rational ENP translation into novel therapeutics for prevention and/or treatment of inflammatory lung disorders.
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/IMJ.40_13197
Publisher: Wiley
Date: 02-1993
Publisher: Wiley
Date: 17-08-2011
Publisher: Elsevier BV
Date: 08-2007
Publisher: Elsevier BV
Date: 12-1998
DOI: 10.1016/S0952-7915(98)80082-4
Abstract: Decreased allergen-specific T cell proliferation and dysregulated cytokine synthesis accompany allergen immunotherapy, consistent with mechanisms of anergy and immune deviation. Recent studies emphasise the pivotal role of decreased T cell IL-4:IFN-gamma ratios. A landmark clinical trial of T cell epitope peptides for venom-immunotherapy shows efficacy and safety murine models suggest intramolecular epitope-suppression inhibits responses to the whole allergen.
Publisher: Elsevier BV
Date: 2018
Publisher: Wiley
Date: 28-05-2013
DOI: 10.1111/CEA.12113
Publisher: Wiley
Date: 11-03-2019
Publisher: Public Library of Science (PLoS)
Date: 06-08-2012
Publisher: Wiley
Date: 10-02-2015
DOI: 10.1038/ICB.2015.4
Abstract: The innate response generated after initial allergen exposure is crucial for polarising adaptive immunity, but little is known about how it drives an atopic or type-2 immune response. The present study characterises the response of skin-draining afferent lymph in sheep following injection with peanut (PN) extract in the presence or absence of aluminium hydroxide (AlOH) adjuvant. Lymph was collected and innate cell populations characterised over an 84 h time period. The innate response to PN extract in afferent lymph displayed an early increase in neutrophils and monocytes without any changes in the dendritic cell (DC) population. PN antigen was transported by neutrophils and monocytes for the first 36 h, after which time DCs were the major antigen trafficking cells. AlOH adjuvant gradually increased antigen uptake by DCs at the later time points. Following lymphatic characterisation, sheep were sensitised with PN extract by three subcutaneous injections of PN in AlOH, and the level of PN-specific immunoglobulin E (IgE) was determined. Sheep with higher levels of steady-state DCs in afferent lymph showed increased monocytic recruitment in afferent lymph and reduced PN-specific IgE following sensitisation. In addition, DCs from afferent lymph that had ingested PN antigen increased the expression of monocyte chemoattractant mRNA. The results of this study show that the innate response to PN extract involves a dynamic change in cell populations in the afferent lymph over time. In addition, DCs may determine the strength of the initial inflammatory cell response, which in turn may determine the nature of the antigen-specific adaptive response.
Publisher: Wiley
Date: 11-01-2005
DOI: 10.1111/J.1398-9995.2005.00663.X
Abstract: Perennial Ryegrass is a major cause of rhinitis in spring and early summer. Bahia grass, Paspalum notatum, flowers late into summer and could account for allergic rhinitis at this time. We determined the frequency of serum immunoglobulin (Ig)E reactivity with Bahia grass in Ryegrass pollen allergic patients and investigated IgE cross-reactivity between Bahia and Ryegrass. Serum from 33 Ryegrass pollen allergic patients and 12 nonatopic donors were tested for IgE reactivity with Bahia and Ryegrass pollen extracts (PE) by enzyme-linked immunosorbent assay (ELISA), western blotting and inhibition ELISA. Allergen-specific antibodies from a pool of sera from allergic donors were affinity purified and tested for IgE cross-reactivity. Seventy-eight per cent of the sera had IgE reactivity with Bahia grass, but more weakly than with Ryegrass. Antibodies eluted from the major Ryegrass pollen allergens, Lol p 1 and Lol p 5, showed IgE reactivity with allergens of Ryegrass and Canary but not Bahia or Bermuda grasses. Timothy, Canary and Ryegrass inhibited IgE reactivity with Ryegrass and Bahia grass, whereas Bahia, Johnson and Bermuda grass did not inhibit IgE reactivity with Ryegrass. The majority of Ryegrass allergic patients also showed serum IgE reactivity with Bahia grass PE. However, Bahia grass and Ryegrass had only limited IgE cross-reactivity indicating that Bahia grass should be considered in diagnosis and treatment of patients with hay fever late in the grass pollen season.
Publisher: Wiley
Date: 10-03-2015
DOI: 10.1038/ICB.2015.7
Publisher: Elsevier BV
Date: 10-1999
Publisher: Proceedings of the National Academy of Sciences
Date: 09-1993
Abstract: Sensitivity to house dust mite antigens in atopic in iduals is a major cause of allergic diseases, ranging from asthma to rhinitis and dermatitis. We have studied the T-cell receptor (TCR) usage of house-dust-mite-specific CD4+ T-cell clones isolated from an atopic in idual, by using the anchored polymerase chain reaction, and have analyzed the peripheral TCR repertoire of the same in idual. Several T-cell clones had identified TCRs at the sequence level, despite the fact that they had been independently isolated, in some cases, in different years. These data suggest the presence in vivo of long-lived T-cell clones. We have also shown that junctional sequences identical to these clones are present in peripheral blood T cells taken 6 years after the isolation of the T-cell clones. The analysis of TCR genes used by the panel of clones reveals oligoclonality, with the variable (V) region gene segments V alpha 8 and V beta 3 being dominant, although there is minimal conservation of junctional sequences. The results have implications for understanding the TCR recognition of an environmental aeroallergen and the life span of T-cell clones in vivo during a chronic immune response.
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.PHARMTHERA.2008.11.007
Abstract: Allergic diseases, including asthma, rhinitis and eczema, represent a major health burden worldwide. Mainstay treatments are allergen avoidance where feasible and pharmacotherapy for symptom relief. For selected patients, allergen-specific immunotherapy (SIT) offers the prospect of long lasting clinical efficacy. SIT involves the administration of allergen extract using a standardized regimen, usually subcutaneously or increasingly sublingually. However, application of this potentially curative treatment is restricted, largely due to the risk of serious adverse events, especially in asthmatics and for potent allergens such as peanut, seafood and latex. New insights into immunological mechanisms underlying effective SIT and molecular characterization of allergens and their recognition by the immune system suggest strategies for refinement of SIT. Selective targeting of allergen-specific T cells, especially regulatory T cells, is likely to be pivotal for efficacy. Recombinant allergens lacking IgE reactivity and small T cell epitope-based peptides are being trialled clinically with evidence of efficacy without serious IgE-mediated adverse reactions. Adjuvants, either co-administered or incorporated into a recombinant allergen vaccine to target tolerogenic dendritic cells may also increase efficacy. The safer sublingual route of allergen administration is attracting interest and different allergen forms may be optimal for inducing tolerance by this route. Defined allergen-derived molecules or peptides offer ease of standardization and, coupled with appropriate targeting of immunoregulatory mechanisms, will result in more widespread clinical use of SIT. Adjunct therapies such as anti-IgE antibody and corticosteroids may minimize the likelihood of adverse reactions in those with severe allergic disease who would most benefit from this treatment.
Publisher: Wiley
Date: 05-2002
DOI: 10.1046/J.1365-2222.2002.01388.X
Abstract: Latex allergy is an important allergic disease for which safe and readily available immunotherapy is currently lacking. Despite advances in latex glove technology and reduction in allergen content, there remains a core of severely allergic health care workers (HCW), particularly with concominant food allergy, for whom allergen avoidance is insufficient. Current experience with immunotherapy using crude latex extracts has shown an unacceptable level of local and systemic side-effects. Latex allergens are extremely potent with a heightened capacity to cross-link effector cell-bound IgE and induce anaphylaxis. The predominant pattern of allergen reactivity among HCW is different from that among children with spina bifida, perhaps due to exposure to latex glove proteins, particularly via inhalation, rather than particle bound latex proteins present in urinary catheters. Recent studies using purified skin testing reagents have indicated that the most clinically important latex allergens amongst HCW are Hev b 5, 6 and 7. Elucidation of the molecular and cellular mechanisms of the immune response to these allergens is pivotal to facilitate the search for safer immunotherapy of latex allergy among HCW.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JACI.2019.06.049
Abstract: The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.
Publisher: Oxford University Press (OUP)
Date: 1994
Abstract: The enterotoxins produced by Staphylococcus aureus are potent mitogens. They stimulate T cells in an oligoclonal fashion that is dependent on the expression of particular variable region gene elements in the beta-chain of the TCR (V beta). The fourth hypervariable loop of the TCR beta-chain is generally regarded as the site of contact for both viral and microbial superantigens. Recently, residues 60 and 61 of staphylococcal enterotoxin B (SEB) have been highlighted as central to the interaction of this toxin with the TCR. We have, therefore, analysed a series of toxins with mutations at these positions to investigate how amino acid substitutions affect the ability of mutant toxins to stimulate both human and mouse T cells. Each of the variant toxins induced proliferation in a murine V beta 8.3 T cell clone, whereas a V beta 8.1 T cell clone only responded to native toxin. A panel of nine human T cell clones expressing six different V beta elements, all of which responded to native SEB, was tested for reactivity to the variant toxins. Only one V beta 19.1+ T cell clone was found to be sensitive to substitution at positions 60 and 61 in a manner analogous to the murine V beta 8.1 T cell clone. Semi-quantitative analysis of the TCR V beta expression of human T cell lines expanded with native and mutant SEB revealed that none of the variant toxins could stimulate T cells that expressed V beta 19.1. Taken together, these results suggest that the interaction of mouse V beta 8.1 and human V beta 19.1 TCRs with SEB differs from other TCRs. Sequence comparisons of the different TCR V beta chains indicated that residues in the second complementarity determining region (CDR2) interact with the 60-61 loop of SEB. Therefore, a minimum of two distinct binding modules confer specificity to the interaction of the TCR with SEB.
Publisher: Wiley
Date: 19-06-2016
DOI: 10.1111/RESP.12831
Abstract: Asthma deaths in Australia are associated with illicit substance abuse, mental health problems and social issues. However, a large proportion of these deaths occurs out of hospital and is difficult to avert by the time the in iduals seek medical attention. We hypothesized that these characteristics may also increase the risk for a patient to require intensive care admission when they present to emergency departments. We studied consecutive patients admitted to a tertiary metropolitan hospital with a primary diagnosis of asthma between January 2010 and January 2014. Clinical and demographical data were obtained from chart review. The patient's postcode was used as a surrogate for socioeconomic status. There were 482 asthma patients admitted during the study period, of which 39 required intensive care. Ten patients admitted to intensive care (26%) used illicit drugs compared with 29 (7%) of those admitted to the ward (adjusted odds ratio: 3.6, P = 0.012). For illicit users, nonadherence to preventer therapy was associated with an even higher risk of intensive care unit admission. Socioeconomic index was lower in the group requiring intensive care admission. The frequency of psychiatric diagnoses was similar in both groups. Among patients admitted to hospital for asthma, illicit substance abuse is a strong independent risk factor for intensive care requirement. Preventer therapy nonadherence further increases this risk. Lower socioeconomic status is also associated with increased risk. These historical features should be actively sought on admission and may serve as useful 'red flags' to prompt consideration of intensive monitoring.
Publisher: Public Library of Science (PLoS)
Date: 19-12-2012
Publisher: Cold Spring Harbor Laboratory
Date: 16-08-2023
DOI: 10.1101/2023.08.15.553357
Abstract: House dust mite (HDM) is the commonest allergen trigger globally for allergic rhinitis and atopic asthma. To expedite accurate confirmation of allergen sensitization, we designed fluorescent allergen tetramers to directly stain specific IgE on basophils to detect allergen sensitization using the flow cytometric CytoBas assay. Recombinant proteins of major HDM allergens (component), Der f 1, Der p 1 and Der p 2 were biotinylated and conjugated with fluorochrome streptavidins as tetramers. Blood s les from 64 HDM-allergic patients and 26 non-HDM-sensitized controls were incubated with allergen tetramers for evaluation of basophil binding (CytoBas) and activation (BAT) with flow cytometry. The tetramers effectively bound and activated basophils from allergic patients but not non-sensitized controls. CytoBas with Der p 1 as a single allergen had comparable sensitivity and specificity (92% and 100%) to BAT (91% and 100%), similarly for CytoBas with a single Der p 2 (95% and 96%) to BAT (95% and 87%) in detecting allergen sensitization. A positive staining for Der p 1 and/or Der p 2 was 100% sensitive and 96% specific for HDM allergy. CytoBas has diagnostic accuracy for group 1 and group 2 HDM allergens that is comparable to a BAT assay, but with additional advantages of multiple allergen components in a single tube and no requirement for in vitro basophil activation. These findings endorse a single, multiplex CytoBas assay for accurate and component-resolved diagnosis of aeroallergen sensitization in patients with allergic asthma and/or rhinitis. A single flow cytometry stain of basophils (CytoBas) with both Der p 1 and Der p 2 provides % specificity and sensitivity for detection of functional HDM allergen sensitization. Fluorescent tetramers of recombinant Der f 1, Der p 1 and Der p 2 can be used to detect functional IgE sensitization to house dust mite (HDM) by flowcytometric detection on basophils (CytoBas). A single CytoBas assay with inclusion of both Der p 1 and Der p 2 can detect HDM sensitization with % sensitivity and specificity.
Publisher: Cold Spring Harbor Laboratory
Date: 04-08-2022
DOI: 10.1101/2022.08.03.502703
Abstract: SARS-CoV-2 vaccination with BNT162b2 (Pfizer BioNTech) has been shown to be 95% effective. 1 Double-dose vaccination generates high levels of spike-specific antibodies, memory B cells (Bmem) and T cells. However, variants of concern (VoC) with mutations in the spike Receptor Binding Domain (RBD) can evade antibody responses. Booster vaccinations improve antibody recognition of VoC, but it is unclear if this is due to higher total antibodies or their capacity to bind VoC. We here addressed the capacity of surface Ig on single Wuhan-specific Bmem after first and second dose BNT162b2 vaccination to recognize variant RBD. S les were collected from 30 healthy COVID-19 naive in iduals pre-BNT162b2 vaccination, 3 weeks post-dose 1 and 4-weeks post-dose 2. Plasma antibodies and Bmem were evaluated using recombinant RBD proteins of the Wuhan, Gamma and Delta strains. All in iduals generated a robust antibody response to BNT162b2 vaccination with all participants producing neutralizing antibodies following dose 2. IgM + and IgG + RBD-specific Bmem were generated after one vaccine dose, and those expressing IgG1 increased in absolute number after dose 2. The majority of RBD-specific Bmem bound the Gamma and/or Delta variants, and this proportion significantly increased after the second dose. The second dose of BNT162b2 increases the number of circulating Ig-class switched RBD-specific Bmem. Importantly, the second dose of vaccination is required for a high frequency of RBD-specific Bmem to recognize Gamma and Delta variants. This suggests that dose 2 not only increases the number of RBD-specific Bmem but also the affinity of the Bmem to overcome the point mutations in VoC.
Publisher: Wiley
Date: 05-02-2008
DOI: 10.1111/J.1365-2222.2008.02941.X
Abstract: Patients with allergic diseases produce an excess of allergen-specific IgE, the specific effector molecule that triggers allergic reactions. The provocation for this excess IgE production is still uncertain. Current ideas include oligoclonal expansion of allergen-specific B cells emanating from germinal centres, activation by superantigen of a subset of B cells, or polyclonal B cells class switching to IgE due to an IL-4 predominance. Additionally, genetic elements contribute to a propensity for increased allergen-specific IgE production. The procedure of RT-PCR allows for lification of infrequent IgE mRNA transcripts from B cells of atopic in iduals, and so facilitates examination of expressed Ig cDNA sequences. Better knowledge of the molecular characteristics of IgE produced by patients with allergic diseases would elucidate the immunogenetic basis for elevated allergen-specific IgE levels. The 'immunogenetic footprint' of IgE transcripts may elucidate the origin and activation of IgE-producing B cells in allergic disease. Here we review studies of the immunogenetic features of IgE in allergic diseases, highlighting the major advances and the experimental limitations.
Publisher: Elsevier BV
Date: 03-2007
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/IMJ.39_13197
Publisher: Hindawi Limited
Date: 11-04-2013
DOI: 10.1155/2013/635695
Abstract: Food allergy is an emerging epidemic that affects all age groups, with the highest prevalence rates being reported amongst Western countries such as the United States (US), United Kingdom (UK), and Australia. The development of animal models to test various food allergies has been beneficial in allowing more rapid and extensive investigations into the mechanisms involved in the allergic pathway, such as predicting possible triggers as well as the testing of novel treatments for food allergy. Traditionally, small animal models have been used to characterise immunological pathways, providing the foundation for the development of numerous allergy models. Larger animals also merit consideration as models for food allergy as they are thought to more closely reflect the human allergic state due to their physiology and outbred nature. This paper will discuss the use of animal models for the investigation of the major food allergens cow's milk, hen's egg, and peanut/other tree nuts, highlight the distinguishing features of each of these models, and provide an overview of how the results from these trials have improved our understanding of these specific allergens and food allergy in general.
Publisher: Wiley
Date: 30-09-2020
DOI: 10.1111/ALL.14582
Publisher: Frontiers Media SA
Date: 15-11-2019
Publisher: Wiley
Date: 03-2021
DOI: 10.1111/ALL.14453
Publisher: European Respiratory Society (ERS)
Date: 12-06-2014
DOI: 10.1183/09031936.00014614
Abstract: The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure 3) aiding risk stratification in chronic disease patients, using a common strategy 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing) 5) proposing a common simulation tool to assist physicians and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
Publisher: Elsevier BV
Date: 2011
Publisher: Elsevier BV
Date: 2002
Publisher: Informa UK Limited
Date: 24-07-2020
Publisher: Wiley
Date: 2002
Publisher: Elsevier BV
Date: 03-1988
Abstract: We compared the bronchodilating effects of intravenously administered enprofylline (2 mg/kg) with nebulized terbutaline (10 mg) in patients presenting to hospital with acute asthma in a multicenter double-blind parallel study. One hundred twenty three patients were randomized into the study, and 69 of these fulfilled the inclusion criteria and a retrospective time to study entry criterion 34 received enprofylline and 35 received terbutaline. There was no significant difference in maximum increase in forced expired volume in 1 second (FEV1) between the enprofylline group (0.24 +/- 0.33 L) and the terbutaline group (0.25 +/- 0.28 L) (p greater than 0.05), nor for the increase in FEV1 over the 1-hour study period. Tremor was reported more in the group receiving terbutaline, and nausea was reported more in the group receiving enprofylline. Two patients experienced hypotension and one patient had a vasovagal episode with enprofylline treatment. Both agents acted as bronchodilators with similar efficacy in patients with acute asthma in this study.
Publisher: European Respiratory Society
Date: 09-2015
Publisher: Elsevier BV
Date: 07-2020
Publisher: Elsevier BV
Date: 05-1994
DOI: 10.1016/0091-6749(94)90383-2
Abstract: The induction of IgE antibodies reactive with the group I allergen of Dermatophagoides species (house dust mite [HDM]), which comprise a major component of the allergic immune response in HDM-atopic in iduals, is dependent on the functional activity of specific CD4+ T cells. In this report we demonstrate that for a particular HDM-atopic in idual the T-cell response to the group I allergen of Dermatophagoides pteronyssinus (Der p I) is limited to a single region (residues 101-143) of the protein. By mapping the fine antigen specificity with T-cell clones, we observed that the sequence 101-131 of Der p I contains a cluster of at least three overlapping T-cell epitopes. Analysis of the HLA class II restriction specificity of the T-cell clones revealed that the T-cell epitope, residues 110-131, was restricted by HLA-DRB1*0101. In contrast, peptide Der p I, 110-119 was recognized in association with HLA-DPB1*0402. However, the ability of cloned T cells to proliferate to the peptide Der p I, 107-119 presented by HLA-DPB1*0401, HLA-DPB1*0402, and HLA-DPB1*0501 expressing accessory cells illustrates the heterogeneity of the restriction specificity of this region of Der p I. The application of this information in the design of peptide-based immunotherapy in the management of allergic responses to HDM is discussed.
Publisher: Wiley
Date: 04-1997
DOI: 10.1111/J.1445-5994.1997.TB00933.X
Abstract: IgE-mediated hypersensitivity to latex proteins has become a significant clinical problem over the last decade. Nursing and medical staff are at risk because of their occupational exposure to latex. To determine the prevalence of type I hypersensitivity to latex allergens in the nursing staff of an Australian hospital. A questionnaire which asked about symptoms associated with the use of latex gloves was completed by 140 nurses working in the Alfred Hospital (72 in general medical wards, 68 in intensive care units). Skin prick tests with eluates of five different types of latex glove as well as common aeroallergens (rye pollen and house dust mite) and banana extract were performed. Thirty-one nurses (22%) were skin prick test positive to at least one of the five latex glove eluates. All of these nurses were atopic, having positive skin prick tests to rye pollen or house dust mite. Symptoms of local dryness, itch and erythema associated with glove use were reported by more than half the study group, but not more frequently by those who were skin prick test positive to latex. Urticaria associated with glove use was reported more frequently by those with positive latex skin prick tests (13% vs 4%, p = 0.05). Eighty-seven per cent of the nurses who were latex skin test positive were also positive to banana extract. IgE-mediated hypersensitivity to latex is common in nurses working in an Australian hospital. Glove associated symptoms were frequently reported, but in most cases the symptoms were more typical of irritant or contact dermatitis rather than type I hypersensitivity reactions. However, the extent of subclinical sensitisation to latex found in this study suggests that symptomatic latex allergy is likely to emerge as an increasing problem for nursing staff in this country.
Publisher: Elsevier
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 08-05-2015
DOI: 10.1007/S00134-015-3822-1
Abstract: To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601] pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57% P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0% P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41] P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65) P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71% P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07) P = 0.33]. EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.
Publisher: Springer Science and Business Media LLC
Date: 16-06-2023
DOI: 10.1007/S10875-023-01527-2
Abstract: Following the COVID-19 pandemic, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe disease may be mediated by immune memory cells. We here evaluated plasma antibody and memory B cells (Bmem) targeting the SARS-CoV-2 Spike receptor-binding domain (RBD) elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, and compared this to the response to mRNA BNT162b2 (Pfizer-BioNTech) vaccination. Whole blood was s led from 31 healthy adults pre-vaccination and 4 weeks after dose one and dose two of ChAdOx1. Neutralizing antibodies (NAb) against SARS-CoV-2 were quantified at each time point. Recombinant RBDs of the Wuhan-Hu-1 (WH1), Delta, BA.2, and BA.5 variants were produced for ELISA-based quantification of plasma IgG and incorporated separately into fluorescent tetramers for flow cytometric identification of RBD-specific Bmem. NAb and RBD-specific IgG levels were over eight times lower following ChAdOx1 vaccination than BNT162b2. In ChAdOx1-vaccinated in iduals, median plasma IgG recognition of BA.2 and BA.5 as a proportion of WH1-specific IgG was 26% and 17%, respectively. All donors generated resting RBD-specific Bmem, which were boosted after the second dose of ChAdOx1 and were similar in number to those produced by BNT162b2. The second dose of ChAdOx1 boosted Bmem that recognized VoC, and 37% and 39% of WH1-specific Bmem recognized BA.2 and BA.5, respectively. These data uncover mechanisms by which ChAdOx1 elicits immune memory to confer effective protection against severe COVID-19.
Publisher: Oxford University Press (OUP)
Date: 1993
Abstract: The group 2 allergens of Dermatophagoides spp. (house dust mite, HDM) are a major immunological target for IgE antibodies in the allergic immune response of HDM atopic in iduals. In this report the heterogeneity of the T cell repertoire reactive with the group 2 allergen of Dermatophagoides pteronyssinus (Der p 2) of a HDM allergic in idual was investigated using overlapping synthetic peptides. By clonal analysis four distinct T cell epitopes were identified, located within residues 16-31, 22-40, 82-100, and 111-129. The importance of these epitopes was confirmed by investigation of the peripheral T cell repertoire, with the polyclonal T cell response to Der p 2 failing to show marked variations in epitope specificity over time. Serological inhibition studies and the use of Epstein-Barr virus transformed B cell lines characterized for their expression of HLA-D region gene products demonstrated that recognition of peptides 16-31 and 111-129 was restricted by HLA-DQ (DQB1*0301), whereas peptide 82-100 is recognized in association with HLA-DR (DRB1*1101). Peptide 22-40 was presented by both HLA-DRB1*1101 and -DQB1*0301 class II molecules. The potential application of these findings lies in the design of peptide-based immunotherapeutics for the management of HDM allergic disease.
Publisher: Wiley
Date: 22-03-2020
DOI: 10.1111/ALL.14204
Abstract: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK‐air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom‐medication scores obtained concurrently. All consecutive MASK‐air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users 205 904 days). Geolocalized users self‐assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom‐medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra‐in idual response variability (IRV) index was calculated. A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom‐medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.
Publisher: Wiley
Date: 20-07-2020
DOI: 10.1111/ALL.14449
Abstract: In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome–related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19–related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease.
Publisher: Wiley
Date: 07-1989
DOI: 10.1111/J.1365-2222.1989.TB02403.X
Abstract: The results of recent experiments investigating the restriction specificity of cross-reactive, or Dermatophagoides farinae-specific, T cell clones isolated from an atopic in idual with perennial rhinitis are reviewed. The restriction specificity was examined using serological inhibition, allogeneic presenting cells and murine fibroblasts expressing HLA-D region products. Although serological inhibition studies suggested that DR class II proteins were the major restriction elements used, the patterns of recognition observed with the allogeneic cell panel were complex, generally failing to correlate with the serologically defined MHC class II specificities. Analysis of the restriction patterns indicated that the majority of the T cell clones were restricted by DR beta III gene products and this was confirmed using murine fibroblasts expressing DRw52. DR beta I gene products functioned as restriction elements in the recognition of house dust mite allergen by the other clones. In an in-vitro model of allergen-dependent IgE synthesis, both DR beta I and DR beta III class II restricted T cells could be shown to provide functional help for IgE synthesized by autologous B cell-enriched populations.
Publisher: American Thoracic Society
Date: 05-1996
DOI: 10.1165/AJRCMB.14.5.8624252
Abstract: The T-cell antigen receptor (TCR) repertoire was examined in lymphocytes isolated from the lungs and blood of 12 sarcoidosis patients and nine control patients. This analysis, by polymerase chain reaction (PCR), examined the variable (V)-domain genes of both the alpha and beta chains of the TCR. This is the first study to examine the usage of all known V alpha gene segments in sarcoidosis. A similar degree of ersity was observed in the TCR repertoire in the lungs and blood of the sarcoidosis patients. However, 11 of the 12 sarcoidosis patients showed an increased use of particular TCR V alpha and V beta genes in lung T cells as compared with blood. The pattern of TCR V gene bias in the lung T cells was specific for each patient. The clonality of selected V genes was examined by determining the third complementarity-determining region (CDR3) length polymorphism of particular PCR products. The majority of lung T cells with biased TCR V gene segments were oligoclonal. Altogether, these results suggest oligoclonal expansion of lung T cells in response to a local antigenic stimulus, with additional nonspecific T-cell accumulation. The variability in the V gene segments used by the expanded T-cell subsets in different sarcoidosis patients may reflect different epitopes or antigens being recognized in the lung, as well as variations in major histocompatibility complex (MHC) haplotype between the patients.
Publisher: AMPCo
Date: 09-2016
DOI: 10.5694/MJA16.00384
Publisher: Frontiers Media SA
Date: 24-04-2019
Publisher: Springer Science and Business Media LLC
Date: 14-01-2016
Publisher: Informa UK Limited
Date: 26-05-2015
DOI: 10.1586/14760584.2015.1050385
Abstract: Allergic diseases are prevalent worldwide. Allergen immunotherapy (AIT) is a current treatment for allergy, leading to modification of the natural course of disease. Mechanisms of efficacy include Treg through release of IL-10 and TGF-β and specific IgG4 blocking antibodies. Subcutaneous and sublingual routes are popular, but uptake is limited by inconvenience and safety concerns. Inclusion criteria limit application to a small proportion of allergic patients. New forms of immunotherapy are being investigated for more efficacious, convenient and safer options with promising advances in recent years. The rationale of reducing vaccine allergenicity to increase safety while improving immunogenicity led to investigation of T-cell epitope-based peptides and recombinant allergen derivatives. Additionally, different routes of administration and adjuvants and adjunct therapies are being explored. This review discusses the current status of AIT and recent advances to improve clinical efficacy, safety and long-term immune tolerance.
Publisher: The American Association of Immunologists
Date: 05-2010
Abstract: Allergy is associated with pathological Th2 responses to otherwise harmless environmental Ags. In contrast, nonallergic in iduals mount nonpathological immune responses to allergens, partly attributed to regulatory T cell (Treg) activity. Although thymus-derived natural Tregs have been shown to maintain tolerance to self-Ags and prevent autoimmunity, the generation of Tregs specific to non–self-Ags is less well understood. We investigated the potential for induction of Tregs from PBMCs of ryegrass pollen-allergic or healthy subjects by stimulation in vitro with ryegrass pollen extract in the absence of additional exogenous stimuli. We found that two subsets of proliferating CD4+ T cells were induced, one expressing intermediate levels of Foxp3 (and IFN-γ, IL-4, IL-17, or IL-2) and the other expressing high levels of Foxp3 (and no effector cytokines). After enrichment based on CD39 expression, the Foxp3hi subset suppressed CD4+ T cell proliferation and IFN-γ production. The Foxp3hi Treg originated from both conversion of iding non-Tregs (CD4+CD25−CD127hi) and expansion of natural Tregs (CD4+CD25+CD127lo). Stable functional Tregs expressing high levels of Foxp3 were induced simultaneously with effector T cells by allergen stimulation. Induction of Foxp3hi Tregs was reduced in allergic subjects. These results indicate that the cogeneration of Foxp3hi Tregs in response to allergen may be a mechanism for controlling allergic reactions in healthy in iduals, which is impaired in those with allergies.
Publisher: Elsevier BV
Date: 02-1999
DOI: 10.1016/S0091-6749(99)70499-9
Abstract: T cells are pivotal in the elicitation of allergic diseases. Analogues of T-cell epitope peptides with a modification at a T-cell receptor (TCR) contact site can alter selected T-cell effector functions. Thus the ability to modulate allergen-specific T-cell responses towards TH1 -like by stimulation with peptide analogues may downregulate allergic inflammation. The purpose of this study was to characterize the minimal epitope recognized by cloned T cells of a dominant Lol p 5 epitope, p105-116, and identify the critical residues involved in TCR and MHC contact. Using peptides with progressive truncation of N- and C-terminal residues in T-cell proliferation assays, we identified the core epitope recognized by cloned CD4(+) T cells. An additional series of peptides with single amino acid substitutions were used in T-cell proliferation and live-cell MHC binding assays. Taken together, these results allowed identification of MHC binding and TCR contact residues of p105-116. The core epitope of p105-116 was identified as residues 107-114. Within this core epitope, 3 residues were found to be important for MHC binding, positions 107, 110, and 112, whereas those at positions 108, 109, 110, 111, and 113 were putative TCR contact residues. The identification of the TCR and MHC contact residues of a dominant Lol p 5 T-cell epitope and analogues of this peptide capable of modulating T-cell responses will allow the evaluation of these peptides' potential as immunotherapeutic agents for rye grass pollen allergic disease.
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.DIAGMICROBIO.2011.09.007
Abstract: Scabies infestations are difficult to diagnose clinically and current serologic tests have less than 50% accuracy. To develop more reliable diagnosis of scabies, specific IgE antibodies to a major scabies antigen recombinant Sar s 14.3 (rSar s 14.3) were measured in 140 plasma s les from scabies-infested and control subject groups using dissociation-enhanced lanthanide fluorescent immunoassays (DELFIA). Levels of rSar s 14.3-specific IgE were quantified, and cross-reactivity with its house dust mite homologue, Der p 14, was assessed. The rSar s 14.3 DELFIA showed excellent diagnostic capability, with 100% sensitivity and 93.75% specificity for distinguishing subjects with current scabies infestation from control, uninfested subjects. Recombinant Der p 14 preparation was ineffective at inhibiting IgE binding to rSar s 14.3. This study shows that quantification of levels of IgE antibody to rSar s 14.3 is a highly sensitive method for diagnosis of scabies infestation in clinical practice.
Publisher: European Respiratory Society (ERS)
Date: 08-03-2018
DOI: 10.1183/13993003.01836-2017
Abstract: Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty. Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking % of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period. Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%). At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies.
Publisher: Elsevier BV
Date: 2009
Publisher: Wiley
Date: 15-09-2015
DOI: 10.1111/CEA.12561
Publisher: Wiley
Date: 23-12-2012
Publisher: Esmon Publicidad, SA
Date: 19-02-2018
DOI: 10.18176/JIACI.0197
Publisher: Cold Spring Harbor Laboratory
Date: 17-02-2020
DOI: 10.1101/2020.02.17.919845
Abstract: Tropomyosins are highly conserved proteins, an attribute that forms the molecular basis for their IgE antibody cross-reactivity. Despite structural similarities, their allergenicity varies greatly between ingested and inhaled invertebrate sources. In this study, we investigated the relationship between the structural stability of different tropomyosins, their endolysosomal degradation patterns and T-cell reactivity. We investigated the differences between four tropomyosins - the major shrimp allergen Pen m 1 and the minor allergens Der p 10 (dust mite), Bla g 7 (cockroach) and Ani s 3 (fish parasite) - in terms of IgE binding, structural stability, endolysosomal degradation and subsequent peptide generation, and T-cell cross-reactivity in a BALB/c murine model. Despite their conserved primary structure and consequent IgE co-reactivity, the invertebrate tropomyosins displayed different protein stabilities. Pen m 1 and Ani s 3, but not Der p 10 and Bla g 7 elicited differential melting temperatures that were pH-dependent. Endolysosomal experiments demonstrated differential degradation, as a function of stability, generating different peptide repertoires. Pen m 1 T-cell clones, with specificity for sequences highly conserved in all four tropomyosins, did not proliferate with Der p 10, Bla g 7 and Ani s 3, indicating that these peptides were not naturally produced for other invertebrate tropomyosins. Our data suggest that, although invertebrate tropomyosins exhibit a high degree of IgE cross-reactivity due to conserved B-cell epitopes, they do not necessarily share identical cross-reactive T-cell epitopes. This is likely due to differential endolysosomal processing as a function of different structural stabilities.
Publisher: Wiley
Date: 03-1991
DOI: 10.1111/J.1365-2222.1991.TB00832.X
Abstract: Staphylococcal enterotoxins are able both to stimulate powerful polyclonal proliferative responses and to induce non-responsiveness of T lymphocytes expressing the appropriate T-cell antigen receptor V beta gene products. T-cell clones representative of the human response to house dust mite were identified that express either V beta 3 or V beta 6 gene products. The specificity of the latter was confirmed by serology. Pre-treatment of cloned V beta 3+ T cells with the Staphylococcus aureus enterotoxins B or C1 rendered them non-responsive to immunogenic challenge with their natural ligand, while retaining responsiveness to exogenous IL-2. Similarly, exposure of the V beta 6+ dust mite reactive T cells to the staphylococcal enterotoxin of the appropriate specificity, SEE, induced specific anergy. The development of non-responsiveness was associated with changes in the T-cell phenotypes. Downregulation of the T-cell receptor, Ti-CD3, was paralleled by enhanced expression of both CD2 and the IL-2 receptor, CD25. Differential co-modulation of CD4 and Ti-CD3 suggested that for some T cells CD4 may form part of the specific antigen recognition structure. Toxicity of the staphylococcal enterotoxins may be removed by chemical modification, thus their ability functionally to inactivate subpopulations of T cells expressing antigen-specific receptors with shared characteristics may be of potential value in the regulation of allergic diseases if the ersity of the T-cell repertoire proves to be limited.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.JACI.2018.08.049
Abstract: Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
Publisher: Wiley
Date: 20-02-2017
Publisher: Wiley
Date: 10-2022
DOI: 10.1111/ALL.15529
Abstract: Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen‐specific IgG 4 . IgG 4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B‐cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen‐specific Bmem subsets induced by SLIT for grass pollen allergy. Blood s les were collected twice outside the pollen season from twenty‐seven patients with sensitization to ryegrass pollen (RGP Lolium perenne ) and seasonal rhinoconjunctivitis. Thirteen received 4‐month pre‐seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single‐cell RNA sequencing was performed on FACS‐purified Lol p 1‐specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort. Four months of SLIT increased RGP‐specific IgE and IgG 4 in serum and induced two Lol p 1‐specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG 4 ), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1 + Bmem expressing surface IgG 4 , CD23, and CD29 after SLIT. A clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface‐expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.
Publisher: Wiley
Date: 04-05-2020
DOI: 10.1111/ALL.14319
Publisher: Wiley
Date: 06-10-2022
DOI: 10.1111/ALL.15526
Abstract: Evaluation of perioperative hypersensitivity (POH) is challenging, and accurate screening tools are needed to optimize the diagnostic process. We aimed to assess and validate the diagnostic value of a published algorithm (using tryptase and clinical presentation) to identify appropriate in iduals for further testing for IgE‐mediated POH. We analysed the clinical presentation (tryptase elevation, cardiovascular, respiratory, skin involvement) of patients proceeding to testing for possible IgE‐mediated POH at a single tertiary referral centre, relative to subsequent skin testing and specific IgE results. Clinical presentations by drug class were also determined. In 293 consecutive patients, the use of a published algorithm based on one or more of (i) defined increase in serum tryptase, (ii) involvement of at least two‐organ systems, or (iii) presentation with new urticaria and/or angioedema was highly sensitive [98.8% (CI95: 95.7–99.9%)] but less specific [34.6% (CI95: 25.7–44.4%)] in identifying patients testing positive on skin testing and/or specific IgE. Presentation with cardiovascular symptoms was also sensitive [89.8%(CI95: 84.2–94.0%)], while the combination of respiratory symptoms and increased tryptase was most specific [85.9%(CI95:76.6–92.5%)]. Respiratory involvement was more common in neuromuscular blocking agent allergy, while urticaria/angioedema was more common in antibiotic allergy. The published algorithm (of tryptase rise, two‐organ involvement or new urticaria/angioedema) is highly sensitive, and appropriate as a screening tool to identify patients suitable for testing for IgE‐mediated POH.
Publisher: Oxford University Press (OUP)
Date: 1991
Abstract: The pathogenesis of joint destruction in rheumatoid arthritis remains ill defined, although it is thought to be the result of tissue damage mediated by T cells. This prompted us to isolate and characterize in vivo activated T cells from rheumatoid arthritis synovial fluid in an attempt to determine their specificity. Heterogeneous synovial fluid cells, containing both adherent and non-adherent cell types, were recovered from joint aspirates and cultured in the presence of IL-2. After 2 weeks, the non-adherent cells were phenotyped as CD3-positive and TCR alpha beta-positive T cells. Polyclonal T cell lines were derived from four rheumatoid arthritis patients of these, two proliferated, in a dose-dependent manner to only autologous synovial fluid in the presence of autologous or DR4Dw4 histocompatible antigen presenting cells. T cell proliferation to the synovial fluid could be inhibited by monomorphic anti-HLA-DR monoclonal antibody, but not by anti-DQ or anti-class I antibodies. T cell clones were established by limiting dilution of a synovial T cell line in the presence of autologous synovial fluid and DR4Dw4 histocompatible accessory cells. Examination of the antigen specificity of these T cell clones demonstrated that they were reactive with a component of synovial fluid. The results of these experiments suggest the presence of an MHC class II-restricted antigen in the rheumatoid arthritis synovial compartment that induces proliferation of in vivo activated T cells.
Publisher: Elsevier BV
Date: 10-1991
DOI: 10.1016/0165-2478(91)90020-B
Abstract: Exotoxins produced by certain strains of Staphylococcus aureus are able to both stimulate and induce non-responsiveness in T cells expressing specific T cell antigen receptor V beta gene elements. The exposure of human CD4+ T cells to the appropriate enterotoxin rendered them anergic to restimulation with their natural ligand, although responsiveness to exogenous IL-2 remained intact. The loss of antigen-dependent proliferation was associated with the down-regulation of the TCR complex that was paralleled by enhanced cell surface CD2 and CD25. Further analysis of the phenotypic changes revealed that membrane levels of CD28 were increased only on activation, suggesting a differential expression of this protein on activated and anergic T cells. During the induction of anergy it was observed that the synthesis of the lymphokines IL-2, IL-4 and IFN-gamma was differentially regulated. IL-4 and IFN-gamma, but not IL-2 were detected in the supernatants of overnight cultures of T cells exposed to tolerising concentrations of toxin. Transcription of IL-4, as determined by polymerase chain reaction at selected intervals, was elevated during the induction of anergy and accounted for the presence of the protein in the supernatants. In contrast, no tight coupling was observed between protein and mRNA levels for IL-2, suggesting post-translational regulation.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.MOLIMM.2019.05.006
Abstract: Shrimp is one of the predominant causes of food allergy among adults, often presenting with severe reactions. Current in vitro diagnostics are based on quantification of patient specific-IgE (sIgE) to shrimp extract. Tropomyosin is the known major shrimp allergen, but IgE sensitisation to other allergens is poorly characterised. In this study, the binding of IgE to various shrimp allergens, additional to tropomyosin, was investigated using sera from 21 subjects who had clinical reactions to one or more shellfish species. Total shrimp-sIgE was quantified using ImmunoCAP, while allergen-sIgEs were quantified using immunoblotting and mass spectrometry, and immuno-PCR to recombinant shrimp tropomyosin. Sixty-two percent of subjects (13/21) were positive to shrimp by ImmunoCAP. IgE from 43% of subjects (9/21) bound tropomyosin, while an additional 29% of subjects (6/21) demonstrated IgE-binding solely to other shrimp allergens, including sarcoplasmic calcium-binding protein, arginine kinase and hemocyanin. Furthermore, IgE sensitisation to other shrimp allergens was demonstrated in 50% of subjects (4/8) who were ImmunoCAP negative. The lack of standardised shrimp allergens and inadequacy of current extracts for shrimp allergy diagnosis is highlighted by this study. Comprehensive knowledge of less studied allergens and their inclusion in component-resolved diagnostics will improve diagnostic accuracy, benefitting the wider population suffering from shellfish allergy.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.JACI.2012.07.053
Abstract: Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent ersistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.
Publisher: Informa UK Limited
Date: 04-2022
DOI: 10.2147/JAA.S304444
Publisher: Bentham Science Publishers Ltd.
Date: 07-2013
DOI: 10.2174/18715230113129990011
Abstract: Allergic diseases including asthma, rhinitis and eczema are known to be a major health and economic burden worldwide. Specific immunotherapy (SIT) is potentially curative but restricted in use, e.g. for asthmatics, due to risk of serious adverse events. Safer, effective SIT preparations require elucidation of mechanisms and immunoregulatory factors. Allergen-specific T cells play a pivotal role. For allergic in iduals, allergen-stimulated T cells largely secrete IL-4, IL-5 and IL-13 (Th2-type cytokines), whereas non-allergics show predominant IFN-γ secretion (Th1-type). Clinically successful SIT is accompanied by altered allergen-specific T cell response, with decreased Th2/Th1 ratio, enhanced IL-10 secretion and regulatory T cell induction. Contributing factors include allergen concentration and form, adjuvant and antigen presenting cell type. In conventional SIT, high dose unfractionated allergen extracts are injected incrementally via the subcutaneous route. To avoid adverse IgE-mediated events but retain efficacy, hypoallergenic T cell-reactive allergen derivatives can be used. These include peptides containing dominant T cell epitopes of allergens, chemically-modified allergens, and recombinant whole or mutant allergens. Such approaches have been evaluated successfully in animal models and early phase clinical trials. Adjuvants and carriers including bacterial and viral components, liposomes and DNA vaccines also promote repolarisation of T cell response and regulatory T cell induction. However caution is needed as excessive IFN- γ secretion may invoke pathogenic inflammation. Sublingual administration has fewer adverse events and is gaining popularity for respiratory allergens, and other routes including intranasal and oral are under evaluation. T cell targeted strategies will facilitate wider clinical application of SIT and reliable laboratory assays for monitoring treatment.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 18-12-2020
DOI: 10.1126/SCIIMMUNOL.ABF8891
Abstract: Memory B cells specific for SARS-CoV-2 spike and nucleocapsid proteins persist in peripheral blood after recovery from COVID-19.
Publisher: Wiley
Date: 09-2003
Publisher: Wiley
Date: 03-1991
DOI: 10.1111/J.1365-3024.1991.TB00268.X
Abstract: In this study the total expenditure on family practitioner services in England was analysed in terms of its distribution between National Health Service regions. Expenditure was then allocated on the basis of estimated regional needs, taking into account the demographic mix of the population and the differentials in health between regions. A comparison between the two regional distributions highlighted the inequalities and inefficiencies in the current system of financing and providing family practitioner services. A coordinated approach to the planning of the separate elements of NHS provision is required which recognizes the interface between primary and secondary health care.
Publisher: Wiley
Date: 07-09-2010
DOI: 10.1111/J.1398-9995.2010.02439.X
Abstract: The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients’ values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.
Publisher: Wiley
Date: 23-10-2021
DOI: 10.1111/ALL.14422
Abstract: Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
Publisher: Wiley
Date: 14-06-2023
DOI: 10.1111/ALL.15754
Publisher: Elsevier BV
Date: 02-1999
DOI: 10.1016/S0161-5890(99)00021-8
Abstract: Hev b 5, a proline-rich acidic protein with a predominantly random secondary structure, is a major allergen in natural rubber latex and a candidate for specific immunotherapy of latex allergy. As a first step in the identification of candidate peptides for immunotherapy, we have begun to identify the B-cell and T-cell epitopes of Hev b 5 in BALB/c mice. The mice were immunized with a Hev b 5 fusion protein. The B-cell epitopes were determined by the SPOTS method using overlapping octamers or by ELISA inhibition using a series of overlapping 20-mers. The T-cell epitopes were determined by the proliferation and cytokine release of splenocytes cultured in the presence of the 20-mers. Potential antibody binding regions included residues in regions 1-38, 55-74, 109-128 and 132-151. Examination of the binding sequences for common motifs suggested enhanced antibody binding to the KXEE or KEXE sequences, where X is empty, threonine or alanine. Splenocyte stimulation and cytokine release suggest T-cell epitopes with the regions 1-20, 37-56, 73-101 and 109-146. Since they may contain major T-cell epitopes but do not exhibit significant antibody binding, peptide regions 38-48 and 75-101 are candidates for specific immunotherapy to Hev b 5 in the BALB/c mouse model.
Publisher: Elsevier BV
Date: 1998
DOI: 10.1016/S0091-6749(98)70206-4
Abstract: Training for the development of cultural competence is often not part of the professional training of nurses within the European Economic Area. Demographic changes in society and the cultural ersity of patients require nurses and other medical staff to provide the highest quality healthcare to patients from different cultural backgrounds. Therefore, nurses must acquire the necessary cultural knowledge, skills, and attitudes as part of their training and professional development to provide culturally competent care to achieve this objective. This review aims to summarize existing methods of developing cultural competence in nurses working in clinical practice. A scoping review of the literature. The following databases were used: PubMed, ScienceDirect, ERIH Plus, and Web of Science using keywords study dates were from 2011 to 2021. The analysis included six studies that met the selection criteria. The studies were categorized as face-to-face, simulations, and online education learning methods. Educational training for cultural competence is necessary for today's nursing. The training content should include real ex les from practice, additional time for self-study using modules, and an assessment of personal attitudes toward cultural differences.
Publisher: Wiley
Date: 09-2003
Publisher: Wiley
Date: 24-08-2018
DOI: 10.1111/ALL.13218
Abstract: The overarching goals of the European Innovation Partnership on Active and Healthy Ageing ( EIP on AHA ) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA ‐France EIP on AHA reference site ( Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology ( ICT ) tools (i.e. the Allergy Diary and CARAT : Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary , (ii) to study the phenotypic characteristics and treatment over a 1‐year period of rhinitis and asthma multimorbidity at baseline (cross‐sectional study) and (iii) to follow‐up using visual analogue scale ( VAS ). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.
Publisher: BMJ
Date: 24-07-2003
Publisher: Wiley
Date: 20-04-2012
Publisher: Wiley
Date: 25-10-2018
Publisher: Elsevier BV
Date: 2000
Publisher: CRC Press
Date: 07-09-2017
Publisher: American Thoracic Society
Date: 15-05-2003
Publisher: Wiley
Date: 08-2003
DOI: 10.1046/J.1445-5994.2003.T01-1-00419.X
Abstract: Subgroups of asthma patients have extremely severe respiratory symptoms that require chronic use of steroids for disease control. These patients are at risk of significant side-effects from chronic exposure to high doses of oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties as shown by its use in some immune disorders. A few trials have suggested a possible benefit in in iduals with severe asthma. To evaluate the role of IVIG as an adjunctive therapy in steroid-dependent asthma, monitoring the outcomes of lung function and measured reduction in oral steroid requirement. Seven patients with severe steroid-dependent asthma were given IVIG at a dose of 1 g/kg each month for 6 months. Baseline pulmonary function tests and immunoglobulin levels were obtained. At the end of 6 months, the end-points observed were lung function and the degree of reduction in the dose of oral steroids. The number of hospital admissions during the 12 months following commencement of IVIG was compared with the preceding 12 months. There was a significant reduction in daily prednisolone dose from 56 +/- 31 mg to 39 +/- 35 mg (P=0.04, Wilcoxon rank sum test) and a decrease in the number of hospital admissions from 5.9 +/- 2.9 to 3.6 +/- 3.5 (P=0.04). No significant improvement occurred in lung function. IVIG provides a potentially important adjunctive therapy in severe steroid-dependent asthma, reducing steroid requirement and decreasing hospital admissions, but not improving lung function.
Publisher: Wiley
Date: 13-01-2014
Abstract: Prawn allergy is one of the leading causes of IgE-mediated hypersensitivity to food. Alterations of IgE-antibody reactivity to prawn allergens due to thermal processing are not fully understood. The aim of this study was to analyze the impact of heating on prawn allergens using a comprehensive allergenomic approach. Proteins from raw and heat-processed black tiger prawn (Penaeus monodon) extracts as well as recombinant tropomyosin (rPen m1) were analyzed by SDS-PAGE and immunoblotting using sera from 16 shellfish allergic patients. IgE antibody binding proteins were identified by advanced mass spectroscopy, characterized by molecular structure analysis and their IgE reactivity compared among the prepared black tiger prawn extracts. Heat processing enhanced the overall patient IgE binding to prawn extracts and increased recognition of a number of allergen variants and fragments of prawn allergens. Allergens identified were tropomyosin, myosin light chain, sarcoplasmic calcium binding protein, and putative novel allergens including triose phosphate isomerase, aldolase, and titin. Seven allergenic proteins are present in prawns, which are mostly heat-stable and form dimers or oligomers. Thermal treatment enhanced antibody reactivity to prawn allergens as well as fragments and should be considered in the diagnosis of prawn allergy and detection of crustacean allergens in processed food.
Publisher: Wiley
Date: 02-03-2010
DOI: 10.1002/JMS.1721
Abstract: The protein tropomyosin (TM) is a known major allergen present in shellfish causing frequent food allergies. TM is also an occupational allergen generated in the working environment of snow crab (Chionoecetes opilio) processing plants. The TM protein was purified from both claw and leg meats of snow crab and analyzed by electrospray ionization and matrix-assisted laser desorption/ionization (MALDI) using hybrid quadruple time-of-flight tandem mass spectrometry (QqToF-MS). The native polypeptide molecular weight of TM was determined to be 32,733 Da. The protein was further characterized using the 'bottom-up' MS approach. A peptide mass fingerprinting was obtained by two different enzymatic digestions and de novo sequencing of the most abundant peptides performed. Any post-translational modifications were identified by searching their calculated and predicted molecular weights in precursor ion spectra. The immunological reactivity of snow crab extract was evaluated using specific antibodies and allergenic reactivity assessed with serum of allergic patients. Subsequently, a signature peptide for TM was identified and evaluated in terms of identity and homology using the basic local alignment search tool (BLAST). The identification of a signature peptide for the allergen TM using MALDI-QqToF-MS will be critical for the sensitive and specific quantification of this highly allergenic protein in the work place.
Publisher: Elsevier BV
Date: 06-2018
Publisher: Springer Science and Business Media LLC
Date: 1989
DOI: 10.2165/00003495-198900371-00006
Abstract: Nedocromil sodium (and sodium cromoglycate) are topical, prophylactic, anti-inflammatory agents used in reversible obstructive airways disease. To investigate their potential mode of action, the effects of these agents on specific allergen- or IL-2-induced proliferation of a human CD4+ house dust mite-specific T-cell clone isolated from an in idual with perennial rhinitis was examined. Although strong proliferation was observed in control cultures, no inhibitory effect was observed with any of the drug concentrations tested. In contrast, dexamethasone was able to inhibit the T-cell proliferation. These observations suggest that the clinically observed suppression of the late-phase asthmatic response may not be due to an effect on CD4+ T lymphocytes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2005
DOI: 10.1097/01.ALL.0000191236.35879.F2
Abstract: The characterization of clinically relevant latex allergens and the production of recombinant allergens is now well advanced, but this knowledge needs to be translated into new strategies for the safe and effective specific treatment of latex allergic diseases including asthma and anaphylaxis. The current status of latex allergy is discussed indicating a changing demographic paradigm. A new wave of latex allergy is emerging outside the healthcare setting with the widespread use of latex products. An increased prevalence in developing countries is also reported. Limited studies on current specific immunotherapy for latex allergy are reviewed, confirming the feasibility but demonstrating an unacceptable risk of adverse events. The characterization of latex allergens and the identification of B and T-cell epitopes point to rational strategies for the generation of hypoallergenic preparations for specific immunotherapy. Results to date for latex allergens are reviewed, including recombinant, chemical modification and synthetic peptide approaches. Candidate hypoallergenic preparations for targeting sensitization to the major allergens Hev b 1, Hev b 3, Hev b 5 and Hev b 6.01 have been identified. Further investigations of optimal regimens for the delivery of specific immunotherapy to induce regulatory T-cell function are warranted. The findings point to the selection of suitable hypoallergenic preparations for clinical trials of effective and safe latex allergy immunotherapy.
Publisher: Wiley
Date: 30-06-2023
DOI: 10.1111/ALL.15740
Abstract: Biomarkers for the diagnosis, treatment and follow‐up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient‐reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real‐life studies and allergen challenges. Using the MASK‐air app as a model, a daily electronic combined symptom‐medication score for allergic diseases (CSMS) or for asthma (e‐DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real‐life, it secondly proposed quality‐of‐life digital biomarkers including daily EQ‐5D visual analogue scales and the bi‐weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.
Publisher: Wiley
Date: 18-06-2020
DOI: 10.1111/ALL.14410
Publisher: Wiley
Date: 26-11-2012
DOI: 10.1111/CEA.12031
Publisher: Elsevier BV
Date: 02-1995
DOI: 10.1016/0198-8859(94)00004-A
Abstract: Stimulation of human CD4+ T-cell clones through the T-cell receptor (TcR) by high doses of specific peptide results in the induction of a long-lived state of nonresponsiveness that has been called anergy. During the induction of anergy, T cells are phenotypically similar to cells responding to an immunogenic stimulus. The amount of TcR at the cell surface is downmodulated, whereas the CD2 and CD25 receptors are increased. When restimulated, however, anergic T cells fail to up-regulate transcription of the IL-2 gene and in consequence do not produce IL-2. In this study, we have compared the ability of various transcription factors to bind to their appropriate site on DNA. Factors were isolated from the nuclei of T cells that were in the induction phase of anergy or were undergoing activation. The pattern of binding activity in restimulated T cells is consistent with the pattern that has previously been shown to regulate T-cell-specific expression of the IL-2 and the beta chain of the TcR genes. The measured binding to a TCF-1 site is the same in the nuclei of resting, activated, and anergized cells. The inducible factors NK-kappa B, beta E2, CD28RC, and AP-1 are not expressed in resting cells and are twofold lower in anergized as compared with activated cells. In contrast, anergic T cells express approximately eightfold lower amounts of NF-AT, a member of the class of inducible factors that regulates IL-2 gene transcription.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Bentham Science Publishers Ltd.
Date: 09-2007
DOI: 10.2174/092986707781696609
Abstract: Allergic diseases constitute a major health issue worldwide. Mainstay treatment constitutes allergen avoidance and pharmacotherapy for symptom relief, but allergen immunotherapy offers advantages of specific treatment with long lasting efficacy, and being able to modify the course of the disease. Conventional immunotherapy involves the subcutaneous injection of gradually increasing amounts of allergen extract but the use of current whole allergen extracts is restricted by the risk of adverse IgE-mediated events especially for potent allergens such as peanut and latex and for asthmatics. This has lead to interest in alternative routes of immunotherapy. Oral tolerance is a well-documented immune process and the sublingual route of administration of allergen immunotherapy is attracting interest. Recent meta-analyses show that sublingual allergen immunotherapy for grass pollen and house dust mite allergy is clinically effective and safer than injection immunotherapy. Some studies show SLIT induces changes of T cell anergy, immune deviation, blocking antibodies, and induction of regulatory T cells, as described for injection immunotherapy pointing to the need to target allergen-specific T cells, there is emergent evidence that the oral mucosa presents distinct regulatory features. Evidence suggests that oral dendritic cells play a key role in inducing tolerance especially when allergen is taken up via Fc receptor bound IgE. This suggests that although both would target allergen-specific T cells, allergen formulations may differ with respect to IgE epitopes for optimal SLIT compared with SCIT. Identification of the molecular nature of the allergen-DC receptor interaction is required to determine whether short peptides or recombinant allergen preparations and of suitable adjuvants specifically tailored for the sublingual route will allow the development of improved allergen formulations and delivery strategies for efficacy of treatment whilst decreasing IgE-mediated adverse effects.
Publisher: Wiley
Date: 20-09-2022
DOI: 10.1111/ALL.15502
Abstract: Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and innovative means to identify infected in iduals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected in iduals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS‐CoV‐2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan‐based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants.
Publisher: Wiley
Date: 07-03-2008
Publisher: Wiley
Date: 30-12-2023
DOI: 10.1111/ALL.15624
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.MOLIMM.2006.02.016
Abstract: Allergy to peanut and tree nuts is characterised by a high frequency of life-threatening anaphylactic reactions and typically lifelong persistence. Although peanut is the most common cause of nut allergy, peanut allergic patients are frequently also sensitive to tree nuts. It is not known if this is due to cross-reactivity between peanut and tree nut allergens. In this study, the major peanut allergen Ara h 2 was cloned from peanut cDNA, expressed in E. coli cells as a His-tag fusion protein and purified using a Ni-NTA column. Immunoblotting, ELISA and basophil activation indicated by CD63 expression all confirmed the IgE reactivity and biological activity of rAra h 2. To determine whether or not this allergen plays a role in IgE cross-reactivity between peanut and tree nuts, inhibition ELISA was performed. Pre-incubation of serum from peanut allergic patients with increasing concentrations of almond or Brazil nut extract inhibited IgE binding to rAra h 2. Purified rAra h 2-specific serum IgE antibodies also bound to proteins present in almond and Brazil nut extracts by immunoblotting. This indicates that the major peanut allergen, Ara h 2, shares common IgE-binding epitopes with almond and Brazil nut allergens, which may contribute to the high incidence of tree nut sensitisation in peanut allergic in iduals.
Publisher: Springer Science and Business Media LLC
Date: 14-06-2006
Abstract: The ADAM33 gene has recently been identified as being a potentially important asthma candidate gene, and polymorphisms in this gene have been shown to be associated with asthma and bronchial hyperresponsiveness in Caucasian in iduals from several populations. We performed chip-based matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry using the MassARRAY system and multiplexed genotyping assays to investigate the association between 10 single nucleotide polymorphisms (SNPs) in the ADAM33 gene (F_+1, Q_-1, S_1, ST_+4, ST_+7, V_-2, V_-1, V_2, V_4, V_5) and asthma and asthma severity in a large Australian Caucasian population of nonasthmatic controls (n = 473), and patients with mild (n = 292), moderate (n = 238) and severe (n = 82) asthma. No significant association was found between any one of the 10 SNPs and asthma or asthma severity, however, there was a significant global haplotypic association with asthma (P = 0.0002) and disease severity (P = 0.0001), driven by the combination of two key SNPs, V_-1 and ST_+7. A meta-analysis of all the genetic studies conducted to date found significant between-study heterogeneity, likely to reflect population stratification. Our analysis of ADAM33 haplotypes further suggests a likely role for ADAM33 in the asthma phenotype, although it does not exclude an association with another locus in linkage disequilibrium with ADAM33.
Publisher: Wiley
Date: 27-06-2006
DOI: 10.1111/J.1365-2222.2006.02523.X
Abstract: Activin A is a member of the transforming growth factor-beta superfamily which is directly implicated in airway structural change and inflammation in asthma. In vitro, the biological effects of activin A are neutralized by the soluble binding protein follistatin. To determine the potential of endogenous follistatin to suppress activin A in vivo by analysing their relative tissue and kinetic compartmentalization during the effector phase of subchronic Th2-driven mucosal inflammation in a murine model of allergic asthma. Eosinophilic mucosal inflammation was elicited by triggering Th2 recall responses by antigen challenge in ovalbumin-sensitized BALB/c mice. The kinetics and distribution of activin A and follistatin protein were assessed in lung tissue and bronchoalveolar lavage fluid and measured in relation to airway eosinophilia, goblet cell metaplasia and Th2 cytokine production in mediastinal lymph nodes. Follistatin was released concurrently with activin A suggesting it acts as an endogenous regulator: peak BAL concentrations coincided with maximal airway eosinophilia, and frequency of IL-4, IL-5 and IL-13 producing cells in mediastinal lymph nodes but induction lagged behind the onset of inflammation. Follistatin and activin A immunoreactivity were lost in airway epithelial cells in parallel with goblet cell metaplasia. Exogenous follistatin inhibited the allergen-specific Th2 immune response in mediastinal lymph nodes and mucus production in the lung. Follistatin is preformed in the normal lung and released in concert with activin A suggesting it serves as an endogenous regulator. Disturbance of the fine balance between activin A and its endogenous inhibitor follistatin may be a determinant of the severity of allergic inflammation or tissue phenotypic shift in asthma.
Publisher: Elsevier BV
Date: 2000
Publisher: Wiley
Date: 24-04-2018
DOI: 10.1111/ALL.13448
Abstract: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden. Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. In a novel approach examining daily symptoms with mobile technology, we found considerable intra-in idual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.
Publisher: Wiley
Date: 08-2005
Publisher: Wiley
Date: 27-05-2020
DOI: 10.1186/S13601-020-00323-0
Abstract: Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.JACI.2015.12.1300
Abstract: This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology the American Academy of Allergy, Asthma & Immunology the American College of Allergy, Asthma and Immunology and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein.
Publisher: Elsevier BV
Date: 06-1991
DOI: 10.1016/0091-6749(91)92158-W
Abstract: Allergic sensitivity of Dermatophagoides spp (house dust mites) is mediated by specific IgE antibody, the production of which requires the presence of CD4+ helper T cells. Attempts to hyposensitize this response in allergic in iduals have depended on the administration of extracts of specific allergen. However, the ability of peptides derived from unrelated antigens to inhibit specific immune responses offers an alternative approach to therapy. We have addressed this question by examining the ability of a nonstimulatory peptide analogue derived from influenza virus hemagglutinin to modulate T cell recognition of house dust mite. The peptide inhibited the response of mite-specific CD4+ T cell clones restricted by either the HLA-DRAB1 or DRAB3 gene products. Furthermore, mite-induced polyclonal T cell responses were negatively modulated by the peptide, whereas recognition of common recall antigens remained intact. The inhibitory effects were mediated at the level of the antigen-presenting cell, since no inhibition of mitogen or anti-CD3 antibody-driven T cell proliferation was observed. In direct binding assays, the peptide analogue bound to selected HLA-DR molecules expressed on the membrane of antigen-presenting cells, with specificity predominantly for those class II proteins capable of restricting house dust mite-allergen T cell recognition.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000321268
Abstract: i Background: /i Peanut and tree nut allergies are life-threatening conditions for many affected in iduals worldwide. Currently there is no cure. While co-allergy to peanut and tree nuts is a common clinical observation, and IgE cross-reactivity between peanut and tree nuts is reported, T cell cross-reactivity is poorly defined. i Methods: /i Hazelnut-specific T cell lines were established using peripheral blood mononuclear cells from 5 subjects with co-allergy to hazelnut and peanut. These lines were stimulated with hazelnut and peanut extracts and purified major peanut allergens, Ara h 1 and Ara h 2. Proliferation was determined by sup /sup H-thymidine incorporation and secretion of key Th1 (IFN-γ) and Th2 (IL-5) cytokines analysed by ELISA. i Results: /i Hazelnut-specific T cell lines from all 5 subjects proliferated upon stimulation with both hazelnut and peanut extracts and for 4 subjects, to Ara h 1 and/or Ara h 2. Proliferating cells were mainly CD4+ T cells and produced both IL-5 and IFN-γ in response to hazelnut and peanut stimulation. Mitogenicity of extracts and allergens was excluded by their lack of stimulation of house dust mite-specific T cells. i Conclusion: /i Our finding that hazelnut and peanut co-allergy is associated with cross-reactive T cell responses, driven partly by cross-reactivity to the major peanut allergens Ara h 1 and Ara h 2, points to future development of allergen immunotherapy by targeting cross-reactive T cells.
Publisher: S. Karger AG
Date: 20-10-2011
DOI: 10.1159/000321821
Abstract: i Background: /i Group 1 grass pollen allergens are glycoproteins of the β-expansin family. They are a predominant component of pollen and are potent allergens with a high frequency of serum IgE reactivity in grass pollen-allergic patients. Bahia grass is distinct from temperate grasses and has a prolonged pollination period and wide distribution in warmer climates. Here we describe the purification of the group 1 pollen allergen, Pas n 1, from Bahia grass i (Paspalum notatum) /i , an important subtropical aeroallergen source. i Methods: /i Pas n 1 was purified from an aqueous Bahia grass pollen extract by ammonium sulphate precipitation, hydrophobic interaction and size exclusion chromatography, and assessed by one- and two-dimensional gel electrophoresis, immunoblotting and ELISA. i Results: /i Pas n 1 was purified to a single 29-kDa protein band containing two dominant isoforms detected by an allergen-specific monoclonal antibody and serum IgE of a Bahia grass pollen-allergic donor. The frequency of serum IgE reactivity with purified Pas n 1 in 51 Bahia grass pollen-allergic patients was 90.6%. Serum IgE reactivity with purified Pas n 1 was highly correlated with serum IgE reactivity with Bahia grass pollen extract and recombinant Pas n 1 (r = 0.821 and 0.913, respectively). i Conclusions: /i Pas n 1 is a major allergen reactive at high frequency with serum IgE of Bahia grass pollen-allergic patients. Purified natural Pas n 1 has utility for improved specific diagnosis and immunotherapy for Bahia grass pollen allergy.
Publisher: Wiley
Date: 21-06-2018
Abstract: Shellfish allergy is an increasing global health priority, frequently affecting adults. Molluscs are an important shellfish group causing food allergy but knowledge of their allergens and cross‐reactivity is limited. Optimal diagnosis of mollusc allergy enabling accurate advice on food avoidance is difficult. Allergens of four frequently ingested Asia‐Pacific molluscs are characterized: Sydney rock oyster ( Saccostrea glomerata ), blue mussel ( Mytilus edulis ), saucer scallop ( Amusium balloti ), and southern calamari ( Sepioteuthis australis ), examining cross‐reactivity between species and with blue swimmer crab tropomyosin, Por p 1. IgE ELISA showed that cooking increased IgE reactivity of mollusc extracts and basophil activation confirmed biologically relevant IgE reactivity. Immunoblotting demonstrated strong IgE reactivity of several proteins including one corresponding to heat‐stable tropomyosin in all species (37–40 kDa). IgE‐reactive Sydney rock oyster proteins were identified by mass spectrometry, and the novel major oyster tropomyosin allergen was cloned, sequenced, and designated Sac g 1 by the IUIS. Oyster extracts showed highest IgE cross‐reactivity with other molluscs, while mussel cross‐reactivity was weakest. Inhibition immunoblotting demonstrated high cross‐reactivity between tropomyosins of mollusc and crustacean species. These findings inform novel approaches for reliable diagnosis and improved management of mollusc allergy.
Publisher: Elsevier BV
Date: 03-2013
Publisher: Wiley
Date: 05-08-2019
DOI: 10.1002/RCR2.464
Publisher: American Thoracic Society
Date: 07-2018
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.NUT.2006.06.002
Abstract: Recent Australian and international legislation requires labeling of wines made by using the potentially allergenic food proteins casein, milk, egg white, or isinglass (fish-derived) where "there is a detectable residual processing aid." We investigated whether wines fined using these proteins or non-grape-derived tannins (tree-nut derived) can provoke significant clinical allergic reactions (anaphylaxis) in patients with confirmed immunoglobulin E-mediated relevant food allergy. A double-blind, placebo-controlled trial was performed to determine whether allergic reactions followed consumption of Australian commercial wines fined using one or more of the legislation-targeted food proteins. In addition, allergenicity of a larger panel of these wines was evaluated by blood basophil activation. No anaphylaxis was induced by wine consumption. Three mild clinical reactions to protein-fined wine and two mild reactions to unfined wine occurred, but there was no statistically significant difference in reaction parameters between subject groups or between processing aids. No pattern of basophil activation correlated with wine type, processing aid, or subject group. Wines fined with egg white, isinglass, or non-grape-derived tannins present an extremely low risk of anaphylaxis to fish-, egg-, or peanut-allergic consumers. Although consumption of milk protein-fined wine did not induce anaphylaxis, there were insufficient subjects to determine statistically whether wines fined with milk proteins present a risk to the very rare milk-allergic consumers. In summary, the observed lack of anaphylaxis and basophil activation induced by wines made using the legislation-targeted food proteins according to good manufacturing practice suggests negligible residual food allergens in these wines.
Publisher: Wiley
Date: 12-1995
DOI: 10.1111/J.1365-2222.1995.TB03039.X
Abstract: The adhesion molecule LFA-1 contributes to the activation response of peripheral blood human CD4+ T cells. Less is known of its contribution to stimulation of long-term CD4+ T cell lines and clones or of its potential to co-stimulate CD4+ T cells of different functional phenotype. This study was therefore performed to investigate co-stimulatory properties of the LFA-1 (CD11a/CD18) complex in the activation of human CD4+ T cell lines and clones of TH-0, TH-1 and TH-2 subsets. Co-stimulatory activity was measured by cross-linking antibodies to CD11a or CD18 with anti-CD3 antibodies to plastic and then measuring the proliferative response of CD4+ T cells to these antibodies. A house duct mite allergen-specific CD4+ T cell line (TH-2) demonstrated much greater dependence on both CD11a and CD18 than a mycobacterial antigen-specific CD4+ T cell line (TH-1). Co-stimulatory activity through LFA-1 was also provided to a house dust mite-specific CD4+ T cell clone (DE-9 TH-2) but not to an influenza haemagglutinin-specific CD4+ T cell clone (HA1-7 TH-0). In contrast, soluble antibodies to CD18 inhibited proliferative responses of both DE-9 and HA1.7 to an immunogenic challenge of antigen and to stimulation by anti-CD3 antibodies. However, the allergen-specific T cells were more susceptible to inhibition. Signal transduction was also observed from the T-cell receptor to LFA-1. Ligation of the T-cell receptor modulated the phenotypic expression of LFA-1 and ICAM-1 on both HA1.7 and DE-9. Phenotypic modulation was observed as a result of both activation and the induction of non-responsiveness. These experiments indicate that CD4+ T cells of TH-2 functional phenotype may have a greater requirement for the co-stimulatory activity of LFA-1 than CD4+ T cells of TH-0 or TH-1 phenotypes.
Publisher: Wiley
Date: 20-08-2018
DOI: 10.1111/CEA.13230
Abstract: Allergic rhinitis (AR) management has changed in recent years following the switch from the concept of disease severity to the concept of disease control, publication of the AR clinical decision support system (CDSS) and development of mobile health (m-health) tools for patients (eg Allergy Diary). The Allergy Diary Companion app for healthcare providers is currently being developed and will be launched in 2018. It incorporates the AR CDSS to provide evidence-based treatment recommendations, linking all key stakeholders in AR management. To produce an electronic version of the AR CDSS (e-CDSS) for incorporation into the Allergy Diary Companion, to describe the app interfaces used to collect information necessary to inform the e-CDSS and to summarize some key features of the Allergy Diary Companion. The steps involved in producing the e-CDSS and incorporating it into the Allergy Diary Companion were (a) generation of treatment management scenarios (b) expert consensus on treatment recommendations (c) generation of electronic decisional algorithms to describe all AR CDSS scenarios (d) digitization of these algorithms to form the e-CDSS and (e) embedding the e-CDSS into the app to permit easy user e-CDSS interfacing. Key experts in the AR field agreed on the AR CDSS approach to AR management and on specific treatment recommendations provided by Allergy Diary Companion. Based on this consensus, decision processes were developed and programmed into the Allergy Diary Companion using Titanium Appcelerator (JavaScript) for IOS tablets. To our knowledge, this is the first time the development of any m-health tool has been described in this transparent and detailed way, providing confidence, not only in the app, but also in the provided management recommendations. The Allergy Diary Companion for providers provides guideline and expert-endorsed AR management recommendations. [MASK paper No 32].
Publisher: S. Karger AG
Date: 2003
DOI: 10.1159/000070924
Abstract: i Background: /i Tree pollen contains many allergens showing cross-reactivity to proteins from pollen, seeds, and fruits of different plant species. Amongst Fagales, responsible for several allergenic responses, hazel provides the best material to study pollen as well as food allergens in one species. The aim of this study was to identify and characterize the physiological function of an allergen from hazel pollen and to determine possible cross-reactivity to proteins from hazelnut. i Methods: /i Monoclonal antibodies (mAbs) against hazel pollen crude extract were produced. On the basis of IgE binding, demonstrated by sera from patients allergic to hazel pollen, one mAb indicating the best correlation has been selected, and the putative allergen was purified by preparative gel electrophoresis. Isoforms were investigated by two-dimensional PAGE, and for molecular identification a hazel pollen cDNA library was constructed. In situ localization of the allergen during pollen development was performed by immunofluorescence labelling. i Results: /i Immunological staining of crude hazel pollen extract with specific IgE and mAb revealed a 70-kD protein. Immunoblot studies with mAb showed cross-reactive proteins of 70–72 kD in different plant tissues and species. After protein purification, the IgE-binding reactivity of the allergen has been reconfirmed, and two isoforms were detected. Molecular cloning identified the allergen as a luminal binding protein (BiP) of the Hsp70 family with 88–92% sequence identity in various plants. Further immunocytological studies indicated involvement of BiP during pollen development. i Conclusions: /i Chaperons like BiP play an important role in protein synthesis and in the protection of cellular structures during stress-related processes. Because of their highly conserved protein sequences, we propose that such allergens could be responsible for at least a part of the allergenic cross-reactivity between proteins from different pollens and plant foods.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.MOLIMM.2014.05.010
Abstract: Fish allergy is a common food allergy, with prevalence rates in the general population ranging between 0.2% and 2.3%. In both adults and children fish ranks in the top eight foods known to cause IgE mediated food allergy. Fish allergy is rarely outgrown and in iduals with fish allergy may be allergic to some but not all species of fish. Whilst fish allergy occurs around the world, the characterization of allergenic components of in idual species of fish has been largely confined to Northern hemisphere and European fish species. To date allergy to commonly consumed fish in the Asian-Pacific region including barramundi (Asian seabass Lates calcarifer) have been less well investigated. The aim of this study was to identify and characterize allergenic proteins from barramundi in both fish allergic adult and pediatric patients. Serum from 17 fish allergic adults and children from Australia were characterized by immunoblotting and enzyme linked immunosorbent assays (ELISA) against raw and heated barramundi. Molecular analysis of identified allergens included genetic sequencing and generation of recombinant isoallergens. Two novel parvalbumin isoforms of the β-type were identified as the only allergens in barramundi and subsequently designated as Lat c 1.0101 and Lat c 1.0201 by the International Union of Immunological Societies. These two isoallergens do not differ in their ability to bind IgE antibodies, but are differentially expressed in barramundi tissue. This study characterized two novel heat stable parvalbumin allergens from barramundi, with differential IgE binding capacity between adults and pediatric patients.
Publisher: Public Library of Science (PLoS)
Date: 22-01-2014
Publisher: Cold Spring Harbor Laboratory
Date: 03-2023
DOI: 10.1101/2023.02.28.530547
Abstract: Following the COVID-19 pandemic caused by SARS-CoV-2, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe disease may be mediated by immune memory cells. We here evaluated plasma antibody and memory B cells (Bmem) targeting the Spike receptor binding domain (RBD) elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, and compared this to the response elicited by the mRNA vaccine BNT162b2 (Pfizer-BioNTech). Whole blood was s led from 31 healthy adults pre-vaccination, and four weeks after dose one and dose two of ChAdOx1. Neutralizing antibodies (NAb) against SARS-CoV-2 were quantified at each timepoint. Recombinant RBDs of the Wuhan-Hu-1 (WH1), Delta, BA.2, and BA.5 variants were produced for ELISA-based quantification of plasma IgG and incorporated separately into fluorescent tetramers for flow cytometric identification of RBD-specific Bmem. NAb and RBD-specific IgG levels were over eight times lower following ChAdOx1 vaccination than BNT162b2. In ChAdOx1-vaccinated in iduals, median plasma IgG recognition of BA.2 and BA.5 as a proportion of WH1-specific IgG was 26% and 17%, respectively. All donors generated resting RBD-specific Bmem, which were boosted after the second dose of ChAdOx1, and were similar in number to those produced by BNT162b2. The second dose of ChAdOx1 boosted Bmem that recognized VoC, and 37% and 39% of WH1-specific Bmem recognized BA.2 and BA.5, respectively. These data uncover mechanisms by which ChAdOx1 elicits immune memory to confer effective protection against severe COVID-19.
Publisher: Wiley
Date: 08-04-2008
DOI: 10.1111/J.1445-5994.2008.01657.X
Abstract: Many patients who describe a history of allergy to penicillin do not prove to be allergic and can be treated safely with penicillin. After a period of 2 years where testing of penicillin allergy was not possible, a new commercial kit has recently become available. We report our initial experience with use of the kit with 29 patients and discuss one patient who experienced anaphylaxis during i.d. testing.
Publisher: American Thoracic Society
Date: 06-2010
Publisher: European Respiratory Society (ERS)
Date: 04-2016
Publisher: Wiley
Date: 06-05-2010
DOI: 10.1111/J.1365-2222.2010.03513.X
Abstract: Seafood plays an important role in human nutrition and health. The growing international trade in seafood species and products has added to the popularity and frequency of consumption of a variety of seafood products across many countries. This increased production and consumption of seafood has been accompanied by more frequent reports of adverse health problems among consumers as well as processors of seafood. Adverse reactions to seafood are often generated by contaminants but can also be mediated by the immune system and cause allergies. These reactions can result from exposure to the seafood itself or various non-seafood components in the product. Non-immunological reactions to seafood can be triggered by contaminants such as parasites, bacteria, viruses, marine toxins and biogenic amines. Ingredients added during processing and canning of seafood can also cause adverse reactions. Importantly all these substances are able to trigger symptoms which are similar to true allergic reactions, which are mediated by antibodies produced by the immune system against specific allergens. Allergic reactions to 'shellfish', which comprises the groups of crustaceans and molluscs, can generate clinical symptoms ranging from mild urticaria and oral allergy syndrome to life-threatening anaphylactic reactions. The prevalence of crustacean allergy seems to vary largely between geographical locations, most probably as a result of the availability of seafood. The major shellfish allergen is tropomyosin, although other allergens may play an important part in allergenicity such as arginine kinase and myosin light chain. Current observations regard tropomyosin to be the major allergen responsible for molecular and clinical cross-reactivity between crustaceans and molluscs, but also to other inhaled invertebrates such as house dust mites and insects. Future research on the molecular structure of tropomyosins with a focus on the immunological and particularly clinical cross-reactivity will improve diagnosis and management of this potentially life-threatening allergy and is essential for future immunotherapy.
Publisher: Springer Science and Business Media LLC
Date: 17-08-2020
Publisher: Elsevier BV
Date: 09-2014
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JACI.2016.03.025
Abstract: The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.
Publisher: Wiley
Date: 12-03-2019
DOI: 10.1111/CEA.13333
Abstract: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
Publisher: Wiley
Date: 08-11-2019
DOI: 10.1111/ALL.14078
Abstract: Allergic diseases are the most common chronic immune‐mediated disorders and can manifest with an enormous ersity in clinical severity and symptoms. Underlying mechanisms for the adverse immune response to allergens and its downregulation by treatment are still being revealed. As a result, there have been, and still are, major challenges in diagnosis, prediction of disease progression/evolution and treatment. Currently, the only corrective treatment available is allergen immunotherapy (AIT). AIT modifies the immune response through long‐term repeated exposure to defined doses of allergen. However, as the treatment usually needs to be continued for several years to be effective, and can be accompanied by adverse reactions, many patients face difficulties completing their schedule. Long‐term therapy also potentially incurs high costs. Therefore, there is a great need for objective markers to predict or to monitor in idual patient's beneficial changes in immune response during therapy so that efficacy can be identified as early as possible. In this review, we specifically address recent technical developments that have generated new insights into allergic disease pathogenesis, and how these could potentially be translated into routine laboratory assays for disease monitoring during AIT that are relatively inexpensive, robust and scalable.
Publisher: Wiley
Date: 29-12-2021
DOI: 10.1111/ALL.14995
Publisher: The American Association of Immunologists
Date: 15-11-2013
Abstract: There is increasing interest in the use of engineered particles for biomedical applications, although questions exist about their proinflammatory properties and potential adverse health effects. Lung macrophages and dendritic cells (DC) are key regulators of pulmonary immunity, but little is known about their uptake of different sized particles or the nature of the induced immunological imprint. We investigated comparatively the immunological imprints of inert nontoxic polystyrene nanoparticles 50 nm in diameter (PS50G) and 500 nm in diameter (PS500G). Following intratracheal instillation into naive mice, PS50G were preferentially taken up by alveolar and nonalveolar macrophages, B cells, and CD11b+ and CD103+ DC in the lung, but exclusively by DC in the draining lymph node (LN). Negligible particle uptake occurred in the draining LN 2 h postinstillation, indicating that particle translocation does not occur via lymphatic drainage. PS50G but not PS500G significantly increased airway levels of mediators that drive DC migration/maturation and DC costimulatory molecule expression. Both particles decreased frequencies of stimulatory CD11b+MHC class IIhi allergen-laden DC in the draining LN, with PS50G having the more pronounced effect. These distinctive particle imprints differentially modulated induction of acute allergic airway inflammation, with PS50G but not PS500G significantly inhibiting adaptive allergen-specific immunity. Our data show that nanoparticles are taken up preferentially by lung APC stimulate cytokine/chemokine production and pulmonary DC maturation and translocate to the lung-draining LN via cell-associated transport. Collectively, these distinctive particle imprints differentially modulate development of subsequent lung immune responses. These findings support the development of lung-specific particulate vaccines, drug delivery systems, and immunomodulators.
Publisher: Wiley
Date: 05-10-2018
DOI: 10.1111/ALL.13307
Abstract: Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.
Publisher: Rockefeller University Press
Date: 11-1993
Abstract: Antigen-specific CD4+ T cells play an important role in the allergic immune response to house dust mite (HDM) allergens in humans. The group 1 allergen of Dermatophagoides spp. is a major target antigen in both B and T cell recognition of HDM. In vitro studies have shown that the presentation of peptides to human T cells under appropriate conditions may lead to a state of specific nonresponsiveness. Therefore, to determine if peptides are able to modulate the function of allergen-reactive T cells in vivo, we have used a murine model of T cell recognition of the HDM allergen Der p 1. The results demonstrate that inhalation of low concentrations of peptide containing the major T cell epitope of Der p 1 (residues 111-139), induces tolerance in naive C57BL/6J mice such that they become profoundly unresponsive to an immunogenic challenge with the intact allergen. When restimulated in vitro with antigen, lymph node T cells isolated from tolerant mice secrete very low levels of interleukin 2, proliferative poorly, and are unable to provide cognate help to stimulate specific antibody production. Furthermore, intranasal peptide therapy was able to inhibit an ongoing immune response to the allergen in mice and this has potential implications in the development of allergen-based immunotherapy.
Publisher: S. Karger AG
Date: 2003
DOI: 10.1159/000075248
Abstract: i Background: /i During clinically effective allergen-specific immunotherapy a shift in cytokine dominance from IL-4, IL-5 predominant to IFN-γ predominant has been observed. As antigen concentration influences Th cell priming, this study aimed to determine the effect of different allergen concentrations on human house dust mite (HDM)-specific T cell production of IL-4 and IFN-γ, proliferation and apoptosis. i Methods: /i HDM-allergic donor PBMC were cultured for 14 days with different concentrations of HDM extract (1, 10 and 100 µg/ml). T cell intracellular IL-4 and IFN-γ, ision (CFSE labelling) and apoptosis (active caspase-3 staining) were analysed by flow cytometry. Proliferation was assessed by sup /sup H-thymidine incorporation. i Results: /i Increased CD4+IFN-γ+ and CD8+IFN-γ+ T cell numbers were observed in high allergen concentration cultures compared with low concentration cultures whereas there were no differences in CD4+IL-4+ and CD8+IL-4+ T cell numbers. CFSE cell labelling revealed that high allergen concentration favours the expansion of IFN-γ-producing CD4+ T cells. The proportion of apoptotic cells increased with allergen concentration and there was preferential apoptosis of CD4+IL-4+ T cells. HDM-induced proliferation was decreased in high allergen concentration cultures this was reversible by IL-2 consistent with anergy. i Conclusion: /i These results show that T cell ision and apoptosis contribute to the cytokine skewing to predominant IFN-γ production by T cells observed at high allergen concentration. Thus the use of hypoallergenic T cell reactive preparations which can be given safely at higher doses than natural extracts may enhance efficacy of allergen-specific immunotherapy.
Publisher: Wiley
Date: 17-08-2016
DOI: 10.1002/CCR3.665
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: No location found
No related grants have been discovered for Robyn O'Hehir.