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B cell repertoire in children with skin barrier dysfunction supports altered IgE maturation associated with allergic food sensitization.

ABSTRACT: The skin is a major immune organ and skin barrier dysfunction is a major risk factor for the development of the inappropriate immune response seen in allergic disease. Skin barrier disruption alters the landscape of antigens experienced by the immune system and the downstream impacts on the antibody repertoire remain poorly characterized, particularly for the IgE isotype responsible for allergic specificity and in early life, when allergic disease is developing. In this study, we sequenced antibody gene repertoires from a large and well-characterized cohort of children with atopic dermatitis and found that food sensitization was associated with lower mutation frequencies in the IgE compartment. This trend was abrogated in children living with pets during the first year of life. These results elucidate potential molecular mechanisms underlying the protective effects of pet ownership and non-antiseptic environs reported for allergic disease, and the hygiene hypothesis more broadly. We also observed increased IgE diversity and increased isotype-switching to the IgE isotype, suggesting that B cell development, particularly isotype-switching, is heavily altered in the those with food allergen sensitizations relative to those without food allergen sensitizations. Unlike for food antigens, aeroallergen sensitization exhibited no effect on IgE mutation or diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization in subjects with atopic dermatitis. Thus, we propose the Immune Repertoire in Atopic Disease (IRAD) score, to quantify this repertoire shift and to aid clinically in patient diagnosis and risk stratification.

SUBMITTER: Gill K

PROVIDER: S-EPMC9915585 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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B cell repertoire of children with atopic dermatitis exhibit altered IgE maturation associated with allergic food sensitization.

Gill Kirandeep K KK Moore Carolina C Nwogu Onyekachi O Kroner John W JW Chang Wan-Chi WC Burkle Jeffrey J Virolainen Samuel J SJ Stevens Mariana L ML Kyzy Asel Baatyrbek AB Miraldi Emily R ER Biagini Jocelyn M JM Devonshire Ashley L AL Kottyan Leah L Schwartz Justin T JT Assa'ad Amal H AH Martin Lisa J LJ Andorf Sandra S Hershey Gurjit K Khurana GKK Roskin Krishna M KM

bioRxiv : the preprint server for biology 20250408

IgE B cells produce antibodies responsible for the inappropriate specificity seen in allergic disease. In this study, we sequence antibody gene repertoires from a large, well-characterized early life cohort at risk for developing food allergy. We found that food allergen sensitization was associated with lower IgE mutation frequencies that was abrogated in children living with a pet dog, suggesting potential molecular mechanisms underlying the hygiene hypothesis (i.e., protective effects of pet ...[more]

PMID: 36778284

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Project description:BackgroundChildren with atopic dermatitis (AD) are often sensitized to food and aeroallergens, but sensitization patterns have not been analysed with biologic measures of disease pathogenicity.ObjectiveWe sought to define allergen sensitization grouping(s) using unbiased machine learning and determine their associations with skin filaggrin (FLG) and transepidermal water loss (TEWL) (assesses skin barrier integrity), S100A8 and S100A9 expression (assesses skin inflammation) and AD severity.MethodsWe studied 400 children with AD in the Mechanisms of Progression from Atopic Dermatitis to Asthma in Children (MPAACH) cohort to identify groupings of food and aeroallergen sensitizations. MPAACH is a paediatric AD cohort, aged 1-2, recruited through hospital/community settings between 2016 and 2018. We analysed these groupings' associations with AD biomarkers: skin FLG, S100A8 and S100A9 expression, total IgE, TEWL and AD severity.ResultsAn unbiased machine learning approach revealed five allergen clusters. The most common cluster (N = 131), SPTPEP, had sensitization to peanut, egg and/or pets. Three low prevalence clusters, which included children with allergen sensitization other than peanut, egg or pets, were combined into SPTOther . SPTNEG included children with no sensitization(s). SPTPEP children had higher median non-lesional TEWL (16.9 g/m2 /h) and IgE (90 kU/L) compared with SPTOTHER (8.8 g/m2 /h and 24 kU/L; p = .01 and p < .001) and SPTNEG (9 g/m2 /h and 26 kU/L; p = .003 and p < .001). SPTPEP children had lower median lesional (0.70) and non-lesional (1.09) FLG expression compared with SPTOTHER (lesional: 0.9; p = .047, non-lesional: 1.78; p = .01) and SPTNEG (lesional: 1.47; p < .001, non-lesional: 2.21; p < .001). There were no differences among groupings in S100A8 or S100A9 expression.Conclusions and clinical relevanceIn this largely clinic-based cohort of young children with AD, allergic sensitization to peanut, egg, cat or dog was associated with more severe disease and skin barrier function but not markers of cutaneous inflammation. These data need replicating in a population-based cohort but may have important implications for understanding the interaction between AD and allergic sensitization.

Dataset Information

B cell repertoire in children with skin barrier dysfunction supports altered IgE maturation associated with allergic food sensitization.

Publications

B cell repertoire of children with atopic dermatitis exhibit altered IgE maturation associated with allergic food sensitization.

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