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Filaggrin loss-of-function mutations are associated with persistence of egg and milk allergy

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Item Type:Article
Title:Filaggrin loss-of-function mutations are associated with persistence of egg and milk allergy
Creators Name:Kalb, B. and Marenholz, I. and Jeanrenaud, A.C. and Meixner, L. and Arnau-Soler, A. and Rosillo-Salazar, O.D. and Ghauri, A. and Cibin, P. and Blümchen, K. and Schlags, R. and Hansen, G. and Seidenberg, J. and Keil, T. and Lau, S. and Niggemann, B. and Beyer, K. and Lee, Y.A.
Abstract:BACKGROUND: A genetic defect in the epidermal barrier protein filaggrin plays a major role in the etiology of eczema and associated allergic airways diseases. However, it is still controversial to what extend loss-of-function (LOF) mutations in the filaggrin gene (FLG) contribute to the development and persistence of food allergies.OBJECTIVE: We tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies. METHODS: We recruited 890 children with challenge-proven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the four most common LOF mutations in FLG; R501X, 2282del4, R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as control population. RESULTS: FLG mutations were associated with allergies to diverse foods including hen's egg (HE), cow's milk (CM), peanut, hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy. CONCLUSION: Using the gold standard for food allergy diagnosis, we demonstrate that FLG LOF mutations confer a risk of any food allergy independent of eczema. They predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development.
Keywords:Persistence, Food Allergy, Hen’s Egg, Cow’s Milk, FLG, Loss-of-Function Mutations, Genetics of Food Allergy Study, GOFA, Double-Blind Placebo-Controlled Food Challenge, Eczema, Animals, Cattle, Chickens
Source:Journal of Allergy and Clinical Immunology
ISSN:0091-6749
Publisher:Elsevier
Volume:150
Number:5
Page Range:1125-1134
Date:November 2022
Official Publication:https://doi.org/10.1016/j.jaci.2022.05.018
PubMed:View item in PubMed

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