ORCID Profile
0000-0002-0009-3337
Current Organisations
UNSW Sydney
,
St Vincent's Hospital Sydney
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Publisher: Edward Elgar Publishing
Date: 27-03-2020
Publisher: Wiley
Date: 16-06-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2016
Publisher: Cold Spring Harbor Laboratory
Date: 31-03-2021
DOI: 10.1101/2021.03.29.21254211
Abstract: There is increasing recognition of the prolonged illness following acute coronavirus disease 2019 (COVID-1). In a longitudinal cohort of 99 patients, 32% reported persistent symptoms and 19% had Long COVID (Defined as fatigue or dyspnoea or chest tightness) at median 240 days after initial infection. There was no significant improvement in symptoms or measures of health-related quality of life between 4 and 8-month assessments. In multivariable analysis, female gender (OR 3.2, 95%CI 1.3-7.8, p=0.01) and acute COVID-19 hospitalisation (OR 3.8, 95% 1.1-13.6, p=0.04) were independently associated with Long COVID at 8-months. Only 80% patients reported full recovery at 8 months. Further research is required to understand the immunologic correlates of abnormal recovery and the long-term significance.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2015
Publisher: Springer Science and Business Media LLC
Date: 30-10-2020
Publisher: Mary Ann Liebert Inc
Date: 12-2021
Publisher: Wiley
Date: 09-05-2017
DOI: 10.1038/ICB.2017.28
Publisher: Elsevier BV
Date: 10-2018
Publisher: Springer Science and Business Media LLC
Date: 09-10-2015
DOI: 10.1038/NCOMMS9495
Abstract: Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of ‘post-treatment control’ (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication.
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1096
Publisher: Springer Science and Business Media LLC
Date: 05-04-2019
DOI: 10.1038/S41598-019-41506-5
Abstract: A HIV vaccine that provides mucosal immunity is urgently needed. We evaluated an intranasal recombinant Fowlpox virus (rFPV) priming vaccine followed by intramuscular Modified Vaccinia Ankara (rMVA) booster vaccine, both expressing SIV antigens. The vaccination generated mucosal and systemic SIV-specific CD4 + T cell mediated immunity and was associated with partial protection against high-dose intrarectal SIV mac251 challenge in outbred pigtail macaques. Three of 12 vaccinees were completely protected and these animals elicited sustained Gag-specific poly-functional, cytotoxic mucosal CD4 + T cells, complemented by systemic poly-functional CD4 + and CD8 + T cell immunity. Humoral immune responses, albeit absent in completely protected macaques, were associated with partial control of viremia in animals with relatively weaker mucosal/systemic T cell responses. Co-expression of an IL-4R antagonist by the rFPV vaccine further enhanced the breadth and cytotoxicity oly-functionality of mucosal vaccine-specific CD4 + T cells. Moreover, a single FPV- gag ol/env prime was able to induce rapid anamnestic gp140 antibody response upon SIV encounter. Collectively, our data indicated that nasal vaccination was effective at inducing robust cervico-vaginal and rectal immunity, although cytotoxic CD4 + T cell mediated mucosal and systemic immunity correlated strongly with ‘complete protection’, the different degrees of protection observed was multi-factorial.
Publisher: Elsevier BV
Date: 04-2023
Publisher: Baishideng Publishing Group Inc.
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 13-01-2022
DOI: 10.1038/S41590-021-01113-X
Abstract: A proportion of patients surviving acute coronavirus disease 2019 (COVID-19) infection develop post-acute COVID syndrome (long COVID (LC)) lasting longer than 12 weeks. Here, we studied in iduals with LC compared to age- and gender-matched recovered in iduals without LC, unexposed donors and in iduals infected with other coronaviruses. Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1) that remained persistently high at 8 months after infection. Using a log-linear classification model, we defined an optimal set of analytes that had the strongest association with LC among the 28 analytes measured. Combinations of the inflammatory mediators IFN-β, PTX3, IFN-γ, IFN-λ2/3 and IL-6 associated with LC with 78.5-81.6% accuracy. This work defines immunological parameters associated with LC and suggests future opportunities for prevention and treatment.
Publisher: Springer International Publishing
Date: 2020
Publisher: IntechOpen
Date: 13-03-2019
Publisher: Frontiers Media SA
Date: 30-07-2015
Publisher: Oxford University Press (OUP)
Date: 19-08-2015
Abstract: Most anal cancers are attributable to persistent human papillomavirus type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), frequently regresses spontaneously. We hypothesized that T-cell responses are associated with HSIL regression. In men who have sex with men undergoing anal cytology and high-resolution anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the CD25/CD134 assay for CD4(+) antigen-specific T cells and intracellular cytokine staining for CD4(+) and CD8(+) antigen-specific T cells. Of 134 participants (mean [SD] age, 51 [9.3] years 31 [23.1%] infected with human immunodeficiency virus), 51 (38.1%) had HSIL. E6- and E7-specific CD4(+) T-cell responses were detected in 80 (59.7%) and 40 (29.9%) of the participants, respectively, and E6- and E7-specific CD8(+) T-cell responses were each detected in 25 (18.7%). HSIL was significantly associated with E7-specific CD8(+) T-cell responses (odds ratio, 4.09 [95% confidence interval, 1.55-10.77], P = .004), but not with any CD4(+) T-cell response (P ≥ .09). Twenty-six participants had HSIL a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were regressors. Five regressors (83%) had E6-specific CD4(+) T-cell responses vs 7 of 20 (35%) nonregressors (Pexact = .065). Systemic HPV-16 E6- and E7-specific T-cell responses were common in men who have sex with men. E6-specific CD4(+) T-cell responses may be associated with recent HSIL regression. NCT02007421.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2019
Publisher: Public Library of Science (PLoS)
Date: 10-05-2017
Publisher: Public Library of Science (PLoS)
Date: 12-2016
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 12-2022
Publisher: Wiley
Date: 25-04-2017
DOI: 10.1038/ICB.2017.15
Publisher: Wiley
Date: 05-02-2016
Publisher: Springer Science and Business Media LLC
Date: 04-10-2018
Publisher: Wiley
Date: 04-2019
DOI: 10.1002/JIA2.25277
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-03-2016
Publisher: Public Library of Science (PLoS)
Date: 25-08-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2017
Publisher: Elsevier BV
Date: 08-2018
Publisher: Wiley
Date: 11-06-2015
DOI: 10.1002/CYTO.A.22704
Abstract: Many methods have been described for automated clustering analysis of complex flow cytometry data, but so far the goal to efficiently estimate multivariate densities and their modes for a moderate number of dimensions and potentially millions of data points has not been attained. We have devised a novel approach to describing modes using second order polynomial histogram estimators (SOPHE). The method ides the data into multivariate bins and determines the shape of the data in each bin based on second order polynomials, which is an efficient computation. These calculations yield local maxima and allow joining of adjacent bins to identify clusters. The use of second order polynomials also optimally uses wide bins, such that in most cases each parameter (dimension) need only be ided into 4-8 bins, again reducing computational load. We have validated this method using defined mixtures of up to 17 fluorescent beads in 16 dimensions, correctly identifying all populations in data files of 100,000 beads in <10 s, on a standard laptop. The method also correctly clustered granulocytes, lymphocytes, including standard T, B, and NK cell subsets, and monocytes in 9-color stained peripheral blood, within seconds. SOPHE successfully clustered up to 36 subsets of memory CD4 T cells using differentiation and trafficking markers, in 14-color flow analysis, and up to 65 subpopulations of PBMC in 33-dimensional CyTOF data, showing its usefulness in discovery research. SOPHE has the potential to greatly increase efficiency of analysing complex mixtures of cells in higher dimensions.
Publisher: Wiley
Date: 13-07-2018
DOI: 10.1111/HIV.12532
Abstract: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L P = 0.02) and triglycerides (difference 0.44 mmol/L P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.
Publisher: Wiley
Date: 05-02-2016
Publisher: Cold Spring Harbor Laboratory
Date: 20-10-2022
DOI: 10.1101/2022.10.19.512954
Abstract: Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells (PBMCs) of convalescent patients using SARS-CoV-2 receptor binding domains (RBDs) carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and class 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (mAb S309) by orders of magnitude. They also provide potent prophylactic and therapeutic in vivo protection of hACE2 mice against viral challenge. Our results indicate that exposure to Wuhan SARS-CoV-2 induces antibodies that maintain potent and broad neutralization against emerging VOCs using two unique strategies: either by targeting the ergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14) or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.
Publisher: Public Library of Science (PLoS)
Date: 10-02-2017
Publisher: Elsevier BV
Date: 2015
DOI: 10.1038/MTNA.2014.67
Publisher: Elsevier BV
Date: 2015
DOI: 10.1038/MTNA.2015.31
Publisher: MDPI AG
Date: 07-12-2016
DOI: 10.3390/GENES7120119
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-05-2015
Publisher: Public Library of Science (PLoS)
Date: 25-08-2016
Publisher: Cold Spring Harbor Laboratory
Date: 22-12-2020
DOI: 10.1101/2020.12.19.20248567
Abstract: The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial s les from 233 RT-PCR-confirmed COVID-19 in iduals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of ‘high responders’ maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design. Neutralizing antibody responses to SARS-CoV-2 are sustained, associated with COVID19 severity, and evaded by emerging viral variants
Publisher: MDPI AG
Date: 12-08-2015
Publisher: Elsevier
Date: 2020
Publisher: Wiley
Date: 06-09-2013
DOI: 10.1111/HIV.12080
Abstract: Anal cancer is one of the most common non-AIDS-defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV-infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV-related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV-infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV-infected adults.
Publisher: Frontiers Media SA
Date: 12-05-2017
Publisher: Elsevier BV
Date: 02-2015
Publisher: Frontiers Media SA
Date: 21-04-2017
Publisher: Public Library of Science (PLoS)
Date: 06-07-2021
DOI: 10.1371/JOURNAL.PMED.1003656
Abstract: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus–cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial s les from 233 reverse transcription polymerase chain reaction (RT-PCR)–confirmed Coronavirus Disease 2019 (COVID-19) in iduals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.
Publisher: Frontiers Media SA
Date: 23-01-2017
Publisher: Springer Science and Business Media LLC
Date: 19-12-2018
DOI: 10.1007/S10461-017-2012-2
Abstract: We assessed trends in HIV testing outcomes during a period of clinic-based initiatives introduced to increase HIV testing among gay and bisexual men (GBM) attending sexual health clinics (SHCs) in New South Wales (NSW). A cohort of 25,487 HIV-negative GBM attending 32 SHCs in NSW (2009-2015) was classified into six sub-groups each year based on client-type (new/existing), risk-status (low/high-risk), and any recent HIV testing. Poisson regression methods were used to assess HIV testing outcomes in sub-groups of GBM. HIV testing outcomes and the sub-groups with greatest statistically significant annual increases were: in iduals attending (26% in high-risk existing clients with recent testing) testing uptake (4% in low-risk existing clients with no recent testing) testing frequency (6% in low-risk existing clients with no recent testing and 5% in high-risk existing clients with recent testing) and total tests (31% in high-risk existing clients with recent testing). High-risk existing clients with recent testing had a 13% annual increase in the proportional contribution to total tests. Our findings show improved targeting of testing to high-risk GBM at NSW SHCs. The clinic-based initiatives should be considered for translation to other similar settings.
Publisher: Elsevier BV
Date: 2019
Publisher: Frontiers Media SA
Date: 24-10-2016
Publisher: Frontiers Media SA
Date: 08-08-2019
Publisher: Springer International Publishing
Date: 2018
Publisher: Oxford University Press (OUP)
Date: 09-09-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1NR08418F
Abstract: A chimeric locked nucleic acid (LNA)–DNA sensor enables hybridization chain reaction (HCR) for the efficient detection and nanoscale imaging of HIV-1 RNA transcripts in cell lysates, and fixed and live cells.
Publisher: MDPI AG
Date: 27-05-2019
DOI: 10.3390/V11050482
Abstract: Australia’s response to the human immunodeficiency virus type 1 (HIV-1) pandemic led to effective control of HIV transmission and one of the world’s lowest HIV incidence rates—0.14%. Although there has been a recent decline in new HIV diagnoses in New South Wales (NSW), the most populous state in Australia, there has been a concomitant increase with non-B subtype infections, particularly for the HIV-1 circulating recombinant form CRF01_AE. This aforementioned CRF01_AE s led in NSW, were combined with those s led globally to identify NSW-specific viral clades. The population growth of these clades was assessed in two-year period intervals from 2009 to 2017. Overall, 109 NSW-specific clades were identified, most comprising pairs of sequences however, five large clades comprising ≥10 sequences were also found. Forty-four clades grew over time with one or two sequences added to each in different two-year periods. Importantly, while 10 of these clades have seemingly discontinued, the remaining 34 were still active in 2016/2017. Seven such clades each comprised ≥10 sequences, and are representative of in idual sub-epidemics in NSW. Thus, although the majority of new CRF01_AE infections were associated with small clades that rarely establish ongoing chains of local transmission, in idual sub-epidemics are present and should be closely monitored.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.VACCINE.2016.09.009
Abstract: Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV.
Publisher: Public Library of Science (PLoS)
Date: 02-07-2015
Publisher: Elsevier BV
Date: 07-2015
Publisher: IEEE
Date: 07-2016
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.JIM.2018.03.007
Abstract: There is growing evidence to support the role of Fc-mediated effector functions, such as Antibody-Dependent Cellular cytotoxicity (ADCC) and Antibody-Dependent Phagocytosis (ADP) in the protection and control of HIV. The RV144 trial and other recent HIV vaccine studies have highlighted the importance of ADCC responses in protection against HIV. The role of neutrophils, the most abundant leukocyte in the blood, has not been thoroughly evaluated for Fc-mediated effector functions to HIV. We optimized HIV-specific neutrophil ADCC and Antibody-Dependent Neutrophil Phagocytosis (ADNP) assays using freshly isolated primary human neutrophils from blood. We also developed methods to study ADP using the neutrophil-like HL-60 cell line. We found that neutrophils mediate both HIV-specific ADP and ADCC responses. In vitro, neutrophil-mediated ADCC responses peaked at 4 h, much faster than primary NK cell or monocyte-mediated responses. We detected a wide range of responses in the ADNP, HL-60 mediated ADP and ADCC across a cohort of 41 viremic antiretroviral therapy naïve HIV positive subjects. HL-60 and Neutrophil-mediated ADP and ADCC responses correlated well with each other, suggesting that they measure overlapping functions. The ADNP and HL-60 ADP inversely correlated with HIV viral load, suggesting that these antibody-mediated neutrophil-based assays should prove useful in dissecting HIV-specific immunity.
Publisher: Mary Ann Liebert Inc
Date: 2019
Publisher: Cold Spring Harbor Laboratory
Date: 07-06-2022
DOI: 10.1101/2022.06.07.22276020
Abstract: Cognitive impairment and function post-acute mild to moderate COVID-19 are poorly understood. We report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung function, physical and mental health were assessed at 2-month post diagnosis. Blood cytokines, neuro-biomarkers, and kynurenine pathway (KP) metabolites were measured at 2-, 4-, 8- and 12- months. Mild to moderate cognitive impairment (demographically corrected) was present in 16%, 23%, and 26%, at 2-, 4- and 12-months post diagnosis, respectively. Overall cognitive performance mildly, but significantly (p .001) declined. Cognitive impairment was more common in those with anosmia (p=.05), but only at 2 months. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly (p .001) associated with cognitive decline. The KP as a unique biomarker offers a potential therapeutic target for COVID-19-related cognitive impairment.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: American Society for Clinical Investigation
Date: 04-2022
DOI: 10.1172/JCI154422
Publisher: Elsevier BV
Date: 02-2019
Publisher: Oxford University Press (OUP)
Date: 11-12-2015
DOI: 10.1093/CID/CIU976
Abstract: The optimal penetration of antiretroviral agents into the central nervous system may be a balance between providing adequate drug exposure to inhibit human immunodeficiency virus (HIV) replication while avoiding concentrations associated with neuronal toxicities. Cerebrospinal fluid (CSF) exposure of efavirenz and the metabolites 7-hydroxy (7OH) and 8-hydroxy (8OH) efavirenz were assessed after at least 12 weeks of therapy in HIV-infected subjects randomized to commence antiretroviral regimens containing efavirenz at either 400 mg or 600 mg once daily. Of 28 subjects (14 and 14 on efavirenz 400 mg and 600 mg, respectively), CSF HIV RNA was undetectable in all. Geometric mean CSF efavirenz, 7OH-, and 8OH-efavirenz concentrations (with 90% confidence intervals [CIs]) for the 400-mg and 600-mg dosing groups were 16.5 (13-21) and 19.5 (15-25) ng/mL 0.6 (.4-.9) and 0.6 (.4-1) ng/mL and 5.1 (4.0-6.4) and 3.1 (2.1-4.4) ng/mL, respectively. Efavirenz concentration in CSF was >0.51 ng/mL (proposed CSF 50% maximal inhibitory concentration for wild-type virus) in all subjects, and 8OH-efavirenz concentration in CSF was >3.3 ng/mL (a proposed toxicity threshold) in 11 of 14 and 7 of 14 subjects randomized to the 400 mg and 600 mg doses of efavirenz, respectively. Whereas CSF efavirenz concentration was significantly associated with plasma concentration (P < .001) and cytochrome P450 2B6 genotype (CSF efavirenz GG to GT/TT geometric mean ratio, 0.56 [90% CI, .42-.74]), CSF 8OH-efavirenz concentration was not (P = .242 for association and CSF 8OH-efavirenz GG to GT/TT geometric mean ratio, 1.52 [90% CI, .97-2.36]). With both doses of efavirenz studied, CSF concentrations were considered adequate to inhibit HIV replication, although concentrations of 8OH-efavirenz were greater than those reportedly associated with neuronal toxicity. CSF exposure of 8OH-efavirenz was not dependent on plasma exposure and, as we postulate, may be subject to saturable pharmacokinetic effects. NCT01011413.
Publisher: Wiley
Date: 04-2018
DOI: 10.1002/JIA2.25109
Publisher: American Society for Microbiology
Date: 15-10-2017
DOI: 10.1128/JVI.00744-17
Abstract: Viruses manipulate the complex interferon and interferon-stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of ISGs in macrophages and dendritic cells, many of which are antiviral. Here, we examine the mechanism of induction of ISGs and show this occurs in two phases. The first phase was transient (0 to 24 h postinfection [hpi]), induced mainly by extracellular vesicles and one of its component proteins, HSP90α, contained within the HIV inoculum. The second, dominant, and persistent phase ( hpi) was induced via newly transcribed HIV RNA and sensed via RIGI, as shown by the reduction in ISG expression after the knockdown of the RIGI adaptor, MAVS, by small interfering RNA (siRNA) and the inhibition of both the initiation and elongation of HIV transcription by short hairpin RNA (shRNA) transcriptional silencing. We further define the induction pathway, showing sequential HIV RNA stimulation via Tat, RIGI, MAVS, IRF1, and IRF7, also identified by siRNA knockdown. IRF1 also plays a key role in the first phase. We also show that the ISGs IFIT1 to -3 inhibit HIV production, measured as extracellular infectious virus. All induced antiviral ISGs probably lead to restriction of HIV replication in macrophages, contributing to a persistent, noncytopathic infection, while the inhibition of interferon facilitates spread to adjacent cells. Both may influence the size of macrophage HIV reservoirs in vivo . Elucidating the mechanisms of ISG induction may help in devising immunotherapeutic strategies to limit the size of these reservoirs. IMPORTANCE HIV, like other viruses, manipulates the antiviral interferon and interferon-stimulated gene (ISG) system to facilitate its initial infection and establishment of viral reservoirs. HIV specifically inhibits all type I and III interferons in its target cells, including macrophages, dendritic cells, and T cells. It also induces a subset of over 20 ISGs of differing compositions in each cell target. This occurs in two temporal phases in macrophages. Extracellular vesicles contained within the inoculum induce the first, transient phase of ISGs. Newly transcribed HIV RNA induce the second, dominant ISG phase, and here, the full induction pathway is defined. Therefore, HIV nucleic acids, which are potent inducers of interferon and ISGs, are initially concealed, and antiviral ISGs are not fully induced until replication is well established. These antiviral ISGs may contribute to persistent infection in macrophages and to the establishment of viral reservoirs in vivo .
Publisher: Springer Science and Business Media LLC
Date: 06-12-2018
DOI: 10.1007/S10461-018-2353-5
Abstract: Adequate adherence to pre-exposure prophylaxis (PrEP) is critical to prevent HIV infection, but accurately measuring adherence remains challenging. We compared two biological [blood drug concentrations in plasma and peripheral blood mononuclear cells (PBMC)] and two self-reported measures (facilitated recall to clinicians and self-report in online surveys) and identified predictors of daily PrEP adherence among gay and bisexual men (GBM) in their first 12 months on PRELUDE, an open-label, single-arm PrEP demonstration project in New South Wales, Australia. 327 participants were enrolled 263 GBM attended their 12-month follow-up visit (81% retention). Overall, 91% of blood s les had plasma drug concentrations indicative of taking 7 pills/week, and 99% had protective drug concentrations (≥ 4 pills/week). Facilitated recall to clinicians identified 99% of participants with protective adherence as measured by PBMC drug concentrations. Daily adherence measured by facilitated recall was associated with behavioural practices including group sex (aOR 1.33, 95% CI 1.15-1.53, p < 0.001). Retained participants maintained high adherence to daily PrEP over 12 months, confirmed by four different measures. Facilitated recall to clinicians is a suitable measure for assessing PrEP adherence in populations engaged in care where there is established trust and rapport with patients. Trial registration: ClinicalTrials.gov NCT02206555.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2020
Publisher: Public Library of Science (PLoS)
Date: 26-10-2015
Publisher: Springer Science and Business Media LLC
Date: 08-11-2019
DOI: 10.1038/S41577-018-0085-4
Abstract: A variety of interventions to induce a functional cure of HIV are being explored, with the aim being to allow patients to cease antiretroviral therapy (ART) for prolonged periods of time or for life. These interventions share the goal of inducing ART-free remission from HIV pathogenesis and disease progression but achieve this in quite different ways, by reducing the size of the latent reservoir (for ex le, small-molecule stimulation of latently infected cells), reducing the number of target cells available for the virus (for ex le, gene therapy) or improving immune responses (for ex le, active or passive immunotherapy). Here, we consider a number of these alternative strategies for inducing post-treatment control of HIV and use mathematical modelling to predict the scale of the challenge inherent in these different approaches. For many approaches, over 99.9% efficacy will likely be required to induce durable ART-free remissions. The efficacy of in idual approaches is currently far below what we predict will be necessary, and new technologies to achieve lifelong functional cure are needed.
Publisher: EDP Sciences
Date: 04-2017
DOI: 10.1051/0004-6361/201629427
Abstract: Context. The addition of a 28 m Cherenkov telescope (CT5) to the H.E.S.S. array extended the experiment’s sensitivityto lower energies. The lowest energy threshold is obtained using monoscopic analysis of data taken with CT5, providing access to gamma-ray energies below 100 GeV for small zenith angle observations. Such an extension of the instrument’s energy range is particularly beneficial for studies of active galactic nuclei with soft spectra, as expected for those at a redshift ≥0.5. The high-frequency peaked BL Lac objects PKS 2155−304 ( z = 0.116) and PG 1553+113 (0.43 z 0.58) are among the brightest objects in the gamma-ray sky, both showing clear signatures of gamma-ray absorption at E 100 GeV interpreted as being due to interactions with the extragalactic background light (EBL). Aims. The aims of this work are twofold: to demonstrate the monoscopic analysis of CT5 data with a low energy threshold, and to obtain accurate measurements of the spectral energy distributions (SED) of PKS 2155−304 and PG 1553+113 near their SED peaks at energies ≈100 GeV. Methods. Multiple observational c aigns of PKS 2155−304 and PG 1553+113 were conducted during 2013 and 2014 using the full H.E.S.S. II instrument (CT1–5). A monoscopic analysis of the data taken with the new CT5 telescope was developed along with an investigation into the systematic uncertainties on the spectral parameters which are derived from this analysis. Results. Using the data from CT5, the energy spectra of PKS 2155−304 and PG 1553+113 were reconstructed down to conservative threshold energies of 80 GeV for PKS 2155−304 , which transits near zenith, and 110 GeV for the more northern PG 1553+113 . The measured spectra, well fitted in both cases by a log-parabola spectral model (with a 5.0 σ statistical preference for non-zero curvature for PKS 2155−304 and 4.5 σ for PG 1553+113 ), were found consistent with spectra derived from contemporaneous Fermi -LAT data, indicating a sharp break in the observed spectra of both sources at E ≈ 100 GeV. When corrected for EBL absorption, the intrinsic H.E.S.S. II mono and Fermi -LAT spectrum of PKS 2155−304 was found to show significant curvature. For PG 1553+113 , however, no significant detection of curvature in the intrinsic spectrum could be found within statistical and systematic uncertainties.
Publisher: The American Association of Immunologists
Date: 10-2016
Publisher: Wiley
Date: 28-11-2022
DOI: 10.1111/IMCB.12606
Abstract: Activation induced marker (AIM) assays are being used increasingly to measure antigen‐specific T‐cell responses, but this activation can alter cell lineage defining phenotypic markers. We aimed to extend the utility of AIM assays to enable pre‐activation defined cell populations to be tracked and quantified within T‐cell memory responses. We sorted three ex vivo CD4 + T‐cell populations prior to any activation using well defined ex vivo lineage surface marker combinations. These populations were memory non‐Tregs, CD39 + Tregs and CD39 neg Tregs, although any three memory CD4 + T‐cell populations able to be isolated by cell surface markers could potentially be tracked. These cells were labeled with three distinct fluorescent cell proliferation dyes (CFSE, CellTrace Violet and Cell Proliferation Dye eF670) and then all autologous PBMCs were reconstituted maintaining ex vivo cell ratios and CD25/OX40 AIM assays performed with CMV and HSV antigens. This approach enabled tracking of pre‐defined cell populations within antigen stimulated responses using both activation marker and cell proliferation readouts. We confirmed that although CD39 + Tregs comprise a substantial proportion of AIM assay responses, they do not make substantial contributions to the proliferative response. This extends the utility of AIM assays to enable parallel analysis of the relative contribution of several CD4 + memory T‐cell subsets to recall responses.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-11-2018
Publisher: Springer Science and Business Media LLC
Date: 13-08-2018
DOI: 10.1007/S10461-018-2247-6
Abstract: Many gay Australian serodiscordant couples are currently relying on an HIV-positive partner's undetectable viral load (UVL) to practice condomless sex. For these couples, preventing HIV is often considered a mutual responsibility, yet they lack a formally endorsed strategy that helps them navigate 'UVL for prevention' (UfP) as a couple. Drawing on interviews with 21 Australian gay men representing 15 serodiscordant couples, we explored 'the couple' within serodiscordant HIV prevention. In learning to rely on UfP, couples were initially apprehensive as they navigated unfamiliar territory, but their concerns faded over time. Confidence in UfP was facilitated by repeated condomless sex without transmission, consistent test results, and being in a couple framed by trust, commitment, and familiarity. Gay male serodiscordant couples should be encouraged to negotiate clear, spoken 'viral load agreements' (VLAs) if they choose to rely on UfP.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.IMMUNI.2015.03.002
Abstract: B helper follicular T (Tfh) cells are critical for long-term humoral immunity. However, it remains unclear how these cells are recruited and contribute to secondary immune responses. Here we show that primary Tfh cells segregate into follicular mantle (FM) and germinal center (GC) subpopulations that display distinct gene expression signatures. Restriction of the primary Tfh cell subpopulation in the GC was mediated by downregulation of chemotactic receptor EBI2. Following collapse of the GC, memory T cells persisted in the outer follicle where they scanned CD169(+) subcapsular sinus macrophages. Reactivation and intrafollicular expansion of these follicular memory T cells in the subcapsular region was followed by their extrafollicular dissemination via the lymphatic flow. These data suggest that Tfh cells integrate their antigen-experience history to focus T cell help within the GC during primary responses but act rapidly to provide systemic T cell help after re-exposure to the antigen.
Publisher: Future Medicine Ltd
Date: 08-2018
Abstract: Australia has maintained a low prevalence of HIV, with a mainly concentrated epidemic and successful public health response. With the widespread availability of HIV genotyping for resistance testing, and development of phylogenetic methodologies, the field of molecular epidemiology has evolved a deeper understanding of ersity and transmission dynamics of HIV. Studies combining HIV genotype with epidemiological data have allowed insights to be gained into the changing subtype ersity, rates of transmitted drug resistance and transmission networks of HIV in Australia. This review provides an overview of HIV molecular epidemiology studies in Australia.
Publisher: Springer Science and Business Media LLC
Date: 22-08-2018
DOI: 10.1038/S41467-018-05772-7
Abstract: Vaccine-induced immunity depends on the generation of memory B cells (MBC). However, where and how MBCs are reactivated to make neutralising antibodies remain unknown. Here we show that MBCs are prepositioned in a subcapsular niche in lymph nodes where, upon reactivation by antigen, they rapidly proliferate and differentiate into antibody-secreting plasma cells in the subcapsular proliferative foci (SPF). This novel structure is enriched for signals provided by T follicular helper cells and antigen-presenting subcapsular sinus macrophages. Compared with contemporaneous secondary germinal centres, SPF have distinct single-cell molecular signature, cell migration pattern and plasma cell output. Moreover, SPF are found both in human and mouse lymph nodes, suggesting that they are conserved throughout mammalian evolution. Our data thus reveal that SPF is a seat of immunological memory that may be exploited to rapidly mobilise secondary antibody responses and improve vaccine efficacy.
Publisher: Springer Science and Business Media LLC
Date: 27-04-2007
Publisher: Elsevier BV
Date: 04-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-11-2016
Publisher: The Company of Biologists
Date: 2016
DOI: 10.1242/JCS.181248
Abstract: Memory T cells are characterised by their rapid transcriptional programs upon re-stimulation. This transcriptional memory (TM) response is facilitated by permissive chromatin but exactly how the permissive epigenetic landscape in memory T cells integrates incoming stimulatory signals remains poorly understood. By genome-wide ChIP-sequencing ex vivo human CD4+ T cells, we show that the signaling enzyme, protein kinase C-theta (PKC-θ) directly relays stimulatory signals to chromatin by binding to TM-responsive genes to induce transcriptional activation. Flanked by permissive histone modifications, these PKC-enriched regions are significantly enriched with NF-κB motifs in ex vivo bulk and vaccinia-responsive human memory CD4+ T cells. Within the nucleus, PKC-θ catalytic activity maintains p65 Ser536 phosphorylation and can directly influence chromatin accessibility at TM genes by regulating H2B deposition via Ser32 phosphorylation. Furthermore, using a cytoplasm-restricted PKC-θ mutant, we highlight chromatin-anchored PKC-θ integrates activating signals at the chromatin template to elicit transcriptional memory responses in human memory T cells.
Publisher: Public Library of Science (PLoS)
Date: 19-10-2017
Publisher: Mary Ann Liebert Inc
Date: 11-2018
Publisher: Springer Science and Business Media LLC
Date: 24-05-2018
Publisher: Springer Science and Business Media LLC
Date: 07-09-2017
DOI: 10.1038/S41598-017-11405-8
Abstract: Liver disease is one of the main contributors to the increased levels of morbidity and mortality seen in the HIV-1-infected, ART-treated population. Circulating miRNAs, particularly those located inside extracellular vesicles, are seen as promising biomarkers for a number of human disease conditions, including liver-related diseases. Here, we show that serum levels of miR-122 and miR-200a are greater in HIV/HCV co-infected in iduals compared to HIV-1 mono-infected in iduals. We also show that miR-122 and miR-200a are elevated in ART-treated, HIV-1-infected in iduals prior to the development of fatal liver disease, suggesting that these miRNA may have some potential clinical utility as biomarkers. While this study is hypothesis generating, it shows clearly that both miR-122 and miR-200a are promising novel biomarkers for liver disease in the ART-treated, HIV-1-infected population.
Publisher: Cold Spring Harbor Laboratory
Date: 09-12-2020
DOI: 10.1101/2020.12.07.20245696
Abstract: Serological testing for SARS-CoV-2 specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence, and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from in iduals recovered from patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n=200), and negative control sera collected prior to the COVID-19 pandemic (n=100) were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) s les. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs IgG vs IgA), and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrate their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation.
Publisher: Wiley
Date: 28-10-2015
DOI: 10.1038/ICB.2014.91
Abstract: Mucosal-associated invariant T (MAIT) cells home to mucosal sites and exert antimicrobial activity against bacteria and other microorganisms. HIV infection leads to early depletion of gut T cells and translocation of bacterial products. There are reports that MAIT cells, defined by coexpression of Vα7.2 and CD161, are depleted during HIV infection and residual MAIT cells are functionally impaired. However, one study suggested that MAIT cells might remain after HIV infection but evade detection through CD161 downregulation. Thus, the impact of HIV infection on MAIT cells is unclear. We studied longitudinal blood s les from 31 HIV-infected subjects for MAIT cell numbers, phenotype and function using both standard Vα7.2/CD161 surface markers and an MR1 tetramer. We found that MAIT cells were depleted early during HIV infection, and although there was a concomitant rise in Vα7.2(+)CD161(-) cells, these were MR1 tetramer negative, indicating that these are unlikely to be altered MAIT cells. Antigen-mediated activation of residual MAIT cells showed that they remained functional out to 2 years following HIV infection. Although MAIT cells are depleted in HIV infection, residual and functionally active MAIT cells persist and may still be able to assist in controlling bacterial translocation during HIV infection.
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1119
Publisher: Frontiers Media SA
Date: 16-09-2015
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JCCT.2016.12.007
Abstract: Epicardial adipose tissue (EAT) is a metabolically active fat depot that is associated with incident coronary artery disease (CAD) and major adverse cardiovascular events. The relationship between EAT and myocardial ischemia remains unclear. This study investigated the relationship between EAT volume and the presence of perfusion defects on myocardial computed tomographic perfusion imaging (CTP) and functional stenoses on invasive fractional flow-reserve (FFR). Data were obtained from a previous prospective cross-sectional study in patients with suspected CAD. Patients underwent combined coronary computed tomography angiography (coronary CTA) and CTP followed by invasive coronary angiogram (ICA) and FFR within 14 days. FFR was performed in all major epicardial vessels unless they were angiographically smooth or occluded, with a threshold of <0.8 considered significant. EAT volume was quantified semi-automatically on coronary CTA. There were 38 patients included for analysis, mean age 62.5 ± 10.0 years, 68.4% male. Median EAT volume was 82.8 mL (interquartile range (IQR) 49.3 mL). FFR was interrogated in 73/114 (64%) vessels. There was no difference in EAT volumes in patients with and without CTP defects (84.4 mL, IQR: 35.6 mL vs 81.1 mL, IQR: 53.1 mL, p = 0.7). There was also no difference in EAT volumes in patients with and without FFR-significant vessels (86.5 mL IQR: 36.6 mL vs 79.1 mL IQR: 54.5 mL, p = 0.7) and no difference when analysed by number of CTP positive territories or FFR-significant vessels (p = 0.4 and p = 0.8 respectively). This study demonstrated no observable relationship between EAT volume and perfusion defects on myocardial CT perfusion imaging or functional stenosis on invasive FFR.
Publisher: Elsevier BV
Date: 10-2015
Publisher: Springer Science and Business Media LLC
Date: 08-02-2023
DOI: 10.1038/S41467-023-36295-5
Abstract: Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the ergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14) or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
Publisher: Wiley
Date: 13-11-2019
Abstract: Semen from HIV-1-infected men contains anti-HIV-1 antibodies and immunosuppressive factor(s). We assessed if suppression of viremia with antiretroviral therapy impacted seminal plasma immunosuppressive capacity or the Fc-dependent functions of seminal anti-HIV-1 antibodies. We also tested if active bacterial sexually transmitted infections altered the immunosuppressive capacity of seminal plasma.
Publisher: Oxford University Press (OUP)
Date: 05-04-2016
DOI: 10.1093/CID/CIW207
Publisher: Wiley
Date: 12-2017
DOI: 10.1111/HIV.12567
Publisher: Palgrave Macmillan US
Date: 2017
Publisher: Elsevier BV
Date: 2016
DOI: 10.1038/MTM.2016.66
Publisher: Mary Ann Liebert Inc
Date: 07-2017
Abstract: HIV-1 reservoirs are most often studied in peripheral blood (PB), but not all lymphocytes recirculate, particularly T follicular helper (Tfh) CD4
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.JACI.2017.02.015
Abstract: Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 This study provides the first estimation of FOXP3
Publisher: Wiley
Date: 05-02-2016
No related grants have been discovered for Anthony Kelleher.