Subproject 4 - Natural resolution factors in tolerance development of food allergy
Project leader Prof. Dr. med. Kirsten Beyer
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Food allergy is a common allergic disease often developing in infancy in parallel with atopic dermatitis. Although many patients will develop clinical tolerance naturally at least one third will suffer from it until adulthood. Oral immunotherapy has been increasingly considered as a treatment option. Our research project will focus on the understanding and prediction of natural and induced tolerance development in children with food allergy. This might help in the future to develop novel preventive and therapeutic strategies by “learning from nature".
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Our principal research question is to understand and predict tolerance development in food allergy. The primary goal of the project is to identify “resolution factors" involved in natural and therapeutically induced tolerance development in children with already established food allergy. This will enable us to understand the mechanism in (1) natural and (2) induced tolerance development and (3) to predict the likelihood of natural tolerance development. We hypothesize
- that the interplay between genetic, epigenetic and environmental factors will influence the immune system and be important for disease resolution, and
- that the microbiome will differ between children with persistent and transient disease.
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In order to understand and compare both, the natural and the induced tolerance development in food allergy, we will focus on two different patient groups:
- The “EFA cohort", which comprise infants and children with and without atopic dermatitis and suspected food allergy who are undergoing oral food challenge for food allergy diagnosis. In this cohort we will investigate the natural tolerance development in order to identify biomarkers as predictors for resolution of food allergy. We will focus on peanut and hen's egg allergy in order to examine allergies with rare and frequent tolerance development.
- The “SOTI cohort", which comprise patients with challenge-proven peanut allergy who underwent oral immunotherapy and are currently in long-term follow-up. In this cohort we will investigate the induced tolerance development.
First step: We aim to identify “natural resolution factors" first cross-sectional comparing patients with known food allergy from the EFA cohort who subsequently gained natural tolerance with those who stayed allergic upon re-challenge.
Second step: We will compare successfully treated peanut allergic patients in long-term follow-up from the SOTI-Cohort (patients who underwent oral immunotherapy) who gained induced tolerance with patients who gained natural tolerance or allergic ones. In this way we will be able to compare the factors involved in induced tolerance development with those involved in natural tolerance development.
Finally in the third step, the same biomarkers will be investigated longitudinally in patients from the EFA cohort to proof the usefulness of the identified biomarkers for prediction.
As main result, the identification of natural and inducible “resolution factors" will enable us to better understand tolerance development in food allergy and to predict the individual time course in food allergic patients. This would allow identifying patients who would profit from immunotherapeutic approaches in the future and the development of novel therapeutic options.
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The team is an interdisciplinary research group with the aim to identify “resolution factors" involved in natural and therapeutically induced tolerance development in food allergy. The group has longstanding expertise in food allergy research and cohort studies and includes physicians, nutritional scientists, biologists, statisticians and epidemiologists from the Department of Pediatric Pneumology and Immunolgy and the Department of Epidemiology of the Charité University as well as the Max-Delbrück Center for Molecular Medicine in Berlin.
The team is an interdisciplinary research group with the aim to identify “resolution factors" involved in natural and therapeutically induced tolerance development in food allergy. The group has longstanding expertise in food allergy research and cohort studies and includes physicians, nutritional scientists, biologists, statisticians and epidemiologists from the Department of Pediatric Pneumology and Immunolgy and the Department of Epidemiology of the Charité University as well as the Max-Delbrück Center for Molecular Medicine in Berlin.Principal Investigator Prof. Dr. med. Kirsten BeyerProf. Dr. med. Kirsten Beyer is Professor of Experimental Pediatrics and trained at the Free University Berlin, the Johns Hopkins University, Baltimore, US and the Mount Sinai School of Medicine, New York, US. She is head of the 'Study Center for Pediatric Allergy' at the 'Department of Pediatric Pneumology and Immunolgy' of the 'Charité Universitätsmedizin Berlin'. Her main clinical focus is pediatric allergy. Her research agenda focuses on the development of better diagnostics, prevention and therapy of food allergy.