Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations

Helen A. Brough, Angela Simpson, Kerry Makinson, Jenny Hankinson, Sara Brown, Abdel Douiri, Danielle C. M. Belgrave, Martin Penagos, Alick C. Stephens, W. H. Irwin McLean, Victor Turcanu, Nicolaos Nicolaou, Adnan Custovic, Gideon Lack (Lead / Corresponding author)

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    Abstract

    Background

    Filaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption.
    Objective

    We sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds.
    Methods

    Exposure to peanut antigen in dust within the first year of life was measured in a population-based birth cohort. Peanut sensitization and peanut allergy (defined by using oral food challenges or component-resolved diagnostics [CRD]) were assessed at 8 and 11 years. Genotyping was performed for 6 FLG mutations.
    Results

    After adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanut dust levels and FLG mutations on peanut sensitization and peanut allergy. Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a more than 6-fold increased odds of peanut SPT sensitization, CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG. There was no significant effect of exposure in children without FLG mutations. In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 0.92 µg of peanut protein per gram (95% CI, 0.70-1.22 µg/g), that for CRD sensitization was 1.03 µg/g (95% CI, 0.90-1.82 µg/g), and that for peanut allergy was 1.17 µg/g (95% CI, 0.01-163.83 µg/g).
    Conclusion

    Early-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation. These data support the hypothesis that peanut allergy develops through transcutaneous sensitization in children with an impaired skin barrier.
    Original languageEnglish
    Pages (from-to)867-875.e1
    Number of pages10
    JournalJournal of Allergy and Clinical Immunology
    Volume134
    Issue number4
    DOIs
    Publication statusPublished - Oct 2014

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    Brough, H. A., Simpson, A., Makinson, K., Hankinson, J., Brown, S., Douiri, A., Belgrave, D. C. M., Penagos, M., Stephens, A. C., McLean, W. H. I., Turcanu, V., Nicolaou, N., Custovic, A., & Lack, G. (2014). Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations. Journal of Allergy and Clinical Immunology, 134(4), 867-875.e1. https://doi.org/10.1016/j.jaci.2014.08.011