Identification and characterization of the IgEome and its role and relevance in food allergy

• Applicant: Dr. Sabine Altrichter
• Subject Area: Clinical Immunology and Allergology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409525714

In food allergy, immunoglobulin E (IgE) antibodies play a major role, but the presence of IgE does not equal clinical allergy, although allergen component resolved diagnostics (CRD) has shed light on patient-specific IgE reactivity. Recent findings indicate that IgE is not solely directed against environmental allergens, but also against endoantigens, which might contribute to the pathogenesis of allergic disease including food allergy. The total IgE with its multiple specificities, against exogenous and endogenous antigens, has been termed the “IgEome”. The IgEome of individual patients changes over time and can be influenced by triggering of the immune system.This project aims to better characterize the role and relevance of the IgEome in food allergy and its prevention and treatment. We hypothesize that the IgEome and its changes, in patients with food allergies and subjects at risk of developing food allergies, are linked to the course of the disease, the outcome of food allergy prevention and treatment, as well as the microbiome. To test this hypothesis, our project will first analyze the IgEome and its changes upon food intervention therapy in children with a high risk of developing food allergy. Specifically, we will establish IgE reactivity profiles for exoantigens and endoantigens before and after food intervention therapy. Baseline IgEomes, post treatment IgEomes, and changes in the IgEomes will then be linked to the intervention and its outcome as well as to the microbiome of the children investigated. Next, we will assess the role and relevance of the IgEome in the treatment of food allergy, i.e. specific immunotherapy, by profiling patients with peanut allergy for their IgE reactivity before and after treatment and correlating their IgEomes and IgEome changes with the outcome. Finally, we will optimize and use cellular activation assays, i.e. the mast cell histamine release assay (MCHRA), to assess IgEomes and their changes for their functional relevance for the management of children at risk of developing food allergies and food allergic patients.The results of this project, i.e. the identification of subtype-specific patient profiles and IgE biomarkers, could help to increase the understanding of the development, prevention and resolution of food allergy. Specific profiles of IgE reactivity could be used to identify patients with a high risk for the developing manifest food allergy and could serve as predictive markers. Importantly, our results may help to optimize the benefit of available prophylactic and therapeutic interventions by providing subtype-specific algorithms and protocols.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 339: Food Allergy and Tolerance (Food@)
• Co-Investigator: Professor Dr. Marcus Maurer (†)