Atopic dermatitis mediates the association between an IL4RA variant and food allergy in school-aged children

Tina M. Banzon, Division of Allergy and Immunology, Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Michael S. Kelly, Harvard Medical School, Boston, MA; Department of Internal Medicine, Massachusetts General Hospital, Boston, MA.
Lisa M. Bartnikas, Division of Allergy and Immunology, Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
William J. Sheehan, Division of Allergy and Immunology, Children's National Hospital, Washington DC; George Washington University School of Medicine and Health Sciences, Washington DC.
Amparito Cunningham, Division of Allergy and Immunology, Boston Children's Hospital, Boston, MA.
Hani Harb, Division of Allergy and Immunology, Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Elena Crestani, Division of Allergy and Immunology, Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Linda Valeri, Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY.
Kimberly F. Greco, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA.
Talal A. Chatila, Division of Allergy and Immunology, Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Wanda Phipatanakul, Division of Allergy and Immunology, Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA; Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA.
Peggy S. Lai, Harvard Medical School, Boston, MA; Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA. Electronic address: PLAI@mgh.harvard.edu.

Document Type

Journal Article

Publication Date

5-16-2022

Journal

The journal of allergy and clinical immunology. In practice

DOI

10.1016/j.jaip.2022.04.042

Keywords

Food allergy (FA); IL4RA; asthma; atopic dermatitis (AD); epicutaneous sensitization; food anaphylaxis; genetics; mediation analysis

Abstract

BACKGROUND: Atopic dermatitis (AD) and food allergy (FA) may share genetic risk factors. It is unknown whether genetic factors directly cause FA or are mediated through AD, as the dual-allergen hypothesis suggests. OBJECTIVE: To test the hypothesis that AD mediates the relationship between an interleukin-4 receptor alpha chain gene (IL4RA) variant, the IL4Rα-R576 polymorphism, and FA. METHODS: 433 children with asthma enrolled in the School Inner-City Asthma Study underwent genotyping for the IL4RA allele. Surveys were administered to determine FA, AD and associated allergic responses. Mediation analysis was performed adjusting for race and ethnicity, age, gender, and household income. Multivariate models were used to determine the association between genotype and FA severity. RESULTS: AD was reported in 193 (45%) and FA in 80 children (19%). Each risk allele increased odds of AD 1.39-fold ([1.03 - 1.87], P = 0.03), and AD increased odds of FA 3.67-fold ([2.05 - 6.57], P < 0.01). There was an indirect effect of genotype, mediated by AD, predicting FA; each risk allele increased the odds of FA by 1.13 (OR [95% CI]: Q/R = 1.13 [1.02 - 1.24], R/R = 1.28 [1.04 - 1.51]; P = <0.01). Each risk allele increased the odds of severe FA symptoms 2.68-fold ([1.26 - 5.71], P = 0.01). CONCLUSION: In a cohort of asthmatic children, AD is part of the causal pathway between an IL4RA variant and FA. This variant is associated with increased risk of severe FA reactions. Addressing AD in children with an IL4RA polymorphism may modulate the risk of FA.

Department

Pediatrics

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