ORCID Profile
0000-0002-8055-0103
Current Organisations
University of Southern Denmark
,
Luxembourg Institute of Health
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Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.IMMUNI.2017.03.019
Abstract: Activated T cells produce reactive oxygen species (ROS), which trigger the antioxidative glutathione (GSH) response necessary to buffer rising ROS and prevent cellular damage. We report that GSH is essential for T cell effector functions through its regulation of metabolic activity. Conditional gene targeting of the catalytic subunit of glutamate cysteine ligase (Gclc) blocked GSH production specifically in murine T cells. Gclc-deficient T cells initially underwent normal activation but could not meet their increased energy and biosynthetic requirements. GSH deficiency compromised the activation of mammalian target of rapamycin-1 (mTOR) and expression of NFAT and Myc transcription factors, abrogating the energy utilization and Myc-dependent metabolic reprogramming that allows activated T cells to switch to glycolysis and glutaminolysis. In vivo, T-cell-specific ablation of murine Gclc prevented autoimmune disease but blocked antiviral defense. The antioxidative GSH pathway thus plays an unexpected role in metabolic integration and reprogramming during inflammatory T cell responses.
Publisher: Wiley
Date: 05-2016
DOI: 10.1111/PAI.12563
Publisher: Wiley
Date: 03-2023
DOI: 10.1111/PAI.13854
Abstract: Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE‐mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE‐mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well‐defined, highly pure molecules for component‐resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for in idual patients. The first edition of the “EAACI Molecular Allergology User's Guide” (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state‐of‐the‐art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.
Publisher: EMBO
Date: 17-01-2022
Publisher: Wiley
Date: 11-01-2012
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: Springer Science and Business Media LLC
Date: 27-07-2015
DOI: 10.1038/NG.3360
Publisher: Wiley
Date: 03-2021
DOI: 10.1111/ALL.14453
Publisher: Elsevier BV
Date: 02-2019
Publisher: Wiley
Date: 15-02-2023
DOI: 10.1111/ALL.15667
Abstract: Allergic diseases and asthma are intrinsically linked to the environment we live in and to patterns of exposure. The integrated approach to understanding the effects of exposures on the immune system includes the ongoing collection of large‐scale and complex data. This requires sophisticated methods to take full advantage of what this data can offer. Here we discuss the progress and further promise of applying artificial intelligence and machine‐learning approaches to help unlock the power of complex environmental data sets toward providing causality models of exposure and intervention. We discuss a range of relevant machine‐learning paradigms and models including the way such models are trained and validated together with ex les of machine learning applied to allergic disease in the context of specific environmental exposures as well as attempts to tie these environmental data streams to the full representative exposome. We also discuss the promise of artificial intelligence in personalized medicine and the methodological approaches to healthcare with the final AI to improve public health.
Publisher: Wiley
Date: 10-04-2023
DOI: 10.1111/ALL.15679
Abstract: Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll‐Like Receptors and IL‐17 for rhinitis alone as a local disease IL‐33 and IL‐5 for allergic and non‐allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono‐ or pauci‐sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.JACI.2011.09.014
Abstract: It was reported that in infants with eczema and food sensitization, the presence of a filaggrin (FLG) null mutation predicts future asthma with a specificity and positive predictive value of 100%. We sought to evaluate the predictive value of food sensitization and food allergy, FLG haploinsufficiency, and their combination in infants with early-onset eczema for persistent eczema and childhood asthma. The German Infant Nutritional Intervention (GINI) and Influence of Lifestyle-related Factors on the Immune System and the Development of Allergies in Childhood (LISA) birth cohorts, as well as a collection of 65 cases of early-onset eczema with and without food allergy were investigated. The risk for asthma was significantly increased by food sensitization (positive diagnostic likelihood ratios [PLRs] of 1.9 [95% CI, 1.1-3.4] in the GINI cohort and 5.5 [95% CI, 2.8-10.8] in the LISA cohort) and the presence of an FLG mutation (PLRs of 2.9 [95% CI, 1.2-6.6] in the GINI cohort and 2.8 [95% CI, 1.0-7.9] in the LISA cohort) with a rather high specificity (79.1% and 92.9% in the GINI cohort and 89.0% and 91.7% in the LISA cohort, respectively) but low sensitivity (40.0% and 39.3% in the GINI cohort and 31.6% and 23.5% in the LISA cohort, respectively). Likewise, the risk for persistent eczema was increased. In the clinical cases neither food allergy nor FLG mutations had a significant effect. The combination of both parameters did not improve prediction and reached positive predictive values of 52.3% (GINI cohort), 66.9% (LISA cohort), and 30.6% (clinical cases), assuming an asthma prevalence in children with early eczema of 30%. Early food sensitization and the presence of an FLG mutation in infants with early eczema increase the risk for later asthma, but the combination of the 2 factors does not represent a clinically useful approach to reliably identify children at risk.
Publisher: Wiley
Date: 04-2021
DOI: 10.1111/ALL.14645
Abstract: Allergic diseases of the (upper and lower) airways, the skin and the gastrointestinal tract, are on the rise, resulting in impaired quality of life, decreased productivity, and increased healthcare costs. As allergic diseases are mostly tissue‐specific, local s ling methods for respective biomarkers offer the potential for increased sensitivity and specificity. Additionally, local s ling using noninvasive or minimally invasive methods can be cost‐effective and well tolerated, which may even be suitable for primary or home care s ling. Non‐ or minimally invasive local s ling and diagnostics may enable a more thorough endotyping, may help to avoid under‐ or overdiagnosis, and may provide the possibility to approach precision prevention, due to early diagnosis of these local diseases even before they get systemically manifested and detectable. At the same time, dried blood s les may help to facilitate minimal‐invasive primary or home care s ling for classical systemic diagnostic approaches. This EAACI position paper contains a thorough review of the various technologies in allergy diagnosis available on the market, which analytes or biomarkers are employed, and which s les or matrices can be used. Based on this assessment, EAACI position is to drive these developments to efficiently identify allergy and possibly later also viral epidemics and take advantage of comprehensive knowledge to initiate preventions and treatments.
Publisher: Public Library of Science (PLoS)
Date: 22-08-2008
Publisher: Wiley
Date: 08-07-2014
DOI: 10.1111/ALL.12406
Publisher: BMJ
Date: 11-2020
DOI: 10.1136/BMJOPEN-2020-041834
Abstract: A few major clinical factors such as sex, obesity or comorbidities have already been associated with COVID-19 severity, but there is a need to identify new epidemiological, clinical, digital and biological characteristics associated with severity and perform deep phenotyping of patients according to severity. The objectives of the Predi-COVID study are (1) to identify new determinants of COVID-19 severity and (2) to conduct deep phenotyping of patients by stratifying them according to risk of complications, as well as risk factors for infection among household members of Predi-COVID participants (the Predi-COVID-H ancillary study). Predi-COVID is a prospective, hybrid cohort study composed of laboratory-confirmed COVID-19 cases in Luxembourg who will be followed up remotely for 1 year to monitor their health status and symptoms. Predi-COVID-H is an ancillary cohort study on household members of index cases included in Predi-COVID to monitor symptoms and household clusters in this high-risk population. A subcohort of up to 200 Predi-COVID and 300 Predi-COVID-H participants with biological s les will be included. Severity of infection will be evaluated by occurrence and duration of hospitalisation, admission and duration of stay in intensive care units or equivalent structures, provision of and duration of supplemental oxygen and ventilation therapy, transfer to another hospital, as well as the impact of infection on daily activities following hospital discharge. The study has been approved by the National Research Ethics Committee of Luxembourg (study number 202003/07) in April 2020. An informed consent is signed by study participants. Scientific articles will be submitted to international peer-reviewed journals, along with press releases for lay audience for major results. NCT04380987 .
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: MDPI AG
Date: 30-11-2022
Abstract: The increasing number of people living with Long COVID requires the development of more personalized care currently, limited treatment options and rehabilitation programs adapted to the variety of Long COVID presentations are available. Our objective was to design an easy-to-use Long COVID classification to help stratify people with Long COVID. In idual characteristics and a detailed set of 62 self-reported persisting symptoms together with quality of life indexes 12 months after initial COVID-19 infection were collected in a cohort of SARS-CoV-2 infected people in Luxembourg. A hierarchical ascendant classification (HAC) was used to identify clusters of people. We identified three patterns of Long COVID symptoms with a gradient in disease severity. Cluster-Mild encompassed almost 50% of the study population and was composed of participants with less severe initial infection, fewer comorbidities, and fewer persisting symptoms (mean = 2.9). Cluster-Moderate was characterized by a mean of 11 persisting symptoms and poor sleep and respiratory quality of life. Compared to the other clusters, Cluster-Severe was characterized by a higher proportion of women and smokers with a higher number of Long COVID symptoms, in particular vascular, urinary, and skin symptoms. Our study evidenced that Long COVID can be stratified into three subcategories in terms of severity. If replicated in other populations, this simple classification will help clinicians improve the care of people with Long COVID.
No related grants have been discovered for Markus W. Ollert.