Pathogenesis of Food Allergy

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

The prevalence of food allergy peaks during the first year of life, but the early life factors that account for the growing number of cases of food allergy in recent decades are poorly understood. Some studies have suggested that lipids may play a role in the development of allergies. In FY22, we collaborated with Dr. Xiaobin Wang at Johns Hopkins University to examine the role of cord blood and maternal plasma levels of triacylglycerols (TAGs) on the development of food allergy. In this study, we were able to identify a TAG profile at birth that could predict the risk of food allergy during childhood. Specifically, we found that infants who had high levels of TAGs consisting of long carbon chains and multiple double bonds in cord blood or in maternal plasma were at lowest risk for developing food allergy, and this association persisted independent of the metabolic status of the mother. This TAG signature was shared across different types of food allergy but was not associated with sensitization to food antigens or with other forms of allergic disease. One of the major limitations in the field of food allergy is the lack of testing modalities that can accurately diagnose food allergy. Patients with atopic dermatitis are especially at risk of having false positive tests to foods because they often have very elevated total IgE levels. We therefore initiated a clinical trial (17-I-0053) to validate diagnostic IgE cut-offs for milk and peanut (and/or their components) that estimate a 50% likelihood of tolerance, a level where oral food challenges are generally offered in clinical practice, in patients with a history of atopic dermatitis and elevated total IgE levels. Despite restrictions on patient visits due to the COVID-19 pandemic, we were able to continue recruitment onto this protocol in FY22 and conducted several oral food challenges to both milk and peanut. In FY22, we additionally established collaborations with organizations and clinics in the DC area to try enhance enrollment of a more diverse population of patients for this study. Another major goal of this project is to understand the basic immunologic pathways that contribute to the pathogenesis of food allergy and other allergic diseases. One approach we have taken to accomplish this goal is to identify rare single gene disorders that strongly predispose (or protect) against the development of allergic disease. During FY22, we continued our investigations into how patients with certain Mendelian disorders, including those harboring mutations in genes targeting the TGFbeta, RUNX1, and PI3K pathways, are strongly predisposed to nearly all forms of allergic disease. This work, utilizing both mouse models and patient samples, is ongoing.