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Early-life inhalant allergen exposure, filaggrin genotype, and the development of sensitization from infancy to adolescence.

Authors
  • Simpson, Angela1
  • Brough, Helen A2
  • Haider, Sadia3
  • Belgrave, Danielle4
  • Murray, Clare S1
  • Custovic, Adnan5
  • 1 Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom. , (United Kingdom)
  • 2 Children's Allergy Service, Evelina London, Guys and St Thomas' NHS Trust, London, United Kingdom; Paediatric Allergy Group, Department of Women and Children's Heath, School of Life Course Sciences, London, United Kingdom; Paediatric Allergy Group, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom. , (United Kingdom)
  • 3 Section of Paediatrics, Imperial College London, United Kingdom; National Heart and Lung Institute, Imperial College London, United Kingdom. , (United Kingdom)
  • 4 Microsoft Research Cambridge, Cambridge, United Kingdom. , (United Kingdom)
  • 5 Section of Paediatrics, Imperial College London, United Kingdom; National Heart and Lung Institute, Imperial College London, United Kingdom. Electronic address: [email protected] , (United Kingdom)
Type
Published Article
Journal
The Journal of allergy and clinical immunology
Publication Date
Mar 01, 2020
Volume
145
Issue
3
Pages
993–1001
Identifiers
DOI: 10.1016/j.jaci.2019.08.041
PMID: 31629803
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

We hypothesized that filaggrin (FLG) loss-of-function mutations modify the effect of allergen exposure on the development of allergic sensitization. We sought to determine whether early-life exposure to inhalant allergens increases the risk of specific sensitization and whether FLG mutations modulate these odds. In a population-based birth cohort we measured mite, cat, and dog allergen levels in dust samples collected from homes within the first year of life. Sensitization was assessed at 6 time points between infancy and age 16 years. Genotyping was performed for 6 FLG mutations. In the longitudinal multivariable model (age 1-16 years), we observed a significant interaction between FLG and Fel d 1 exposure on cat sensitization, with the effect of exposure being significantly greater among children with FLG mutations compared with those without (odds ratio, 1.36; 95% CI, 1.02-1.80; P = .035). The increase in risk of mite sensitization with increasing Der p 1 exposure was consistently greater among children with FLG mutations, but the interaction did not reach statistical significance. Different associations were observed for dogs: there was a significant interaction between FLG and dog ownership, but the risk of sensitization to any allergen was significantly lower among children with FLG mutations who were exposed to a dog in infancy (odds ratio, 0.16; 95% CI, 0.03-0.86; P = .03). FLG loss-of-function mutations modify the relationship between allergen exposure and sensitization, but effects differ at different ages and between different allergens. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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