Early-life inhalant allergen exposure, filaggrin genotype and the development of sensitization from infancy to adolescence
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
We hypothesized that filaggrin loss-of-function mutations modify the impact of allergen exposure on the development of allergic sensitization.
Objective
To determine whether early-life exposure to inhalant allergens increases the risk of specific sensitization, and whether filaggrin mutations modulate these odds.
Methods
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 six filaggrin mutations.
Results
In the longitudinal multivariable model (age 1-16 years), we observed a significant interaction between filaggrin and Fel d 1 exposure on cat sensitization, with the effect of exposure being significantly greater among children with filaggrin mutations compared to those without (OR 1.36, 95% CI 1.02-1.80, p=0.035). The increase in risk of mite sensitization with increasing Der p 1 exposure was consistently higher among children with filaggrin mutations, but the interaction did not reach statistical significance. Different association were observed for dog: there was a significant interaction between filaggrin and dog ownership, but the risk of sensitization to any allergen was significantly lower among children with filaggrin mutations who were exposed to dog in infancy (OR 0.16, 95% CI 0.03–0.86, p=0.03).
Conclusions
Filaggrin loss-of function mutations modify the relationship between allergen exposure and sensitization, but effects differ at different ages and between different allergens.
We hypothesized that filaggrin loss-of-function mutations modify the impact of allergen exposure on the development of allergic sensitization.
Objective
To determine whether early-life exposure to inhalant allergens increases the risk of specific sensitization, and whether filaggrin mutations modulate these odds.
Methods
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 six filaggrin mutations.
Results
In the longitudinal multivariable model (age 1-16 years), we observed a significant interaction between filaggrin and Fel d 1 exposure on cat sensitization, with the effect of exposure being significantly greater among children with filaggrin mutations compared to those without (OR 1.36, 95% CI 1.02-1.80, p=0.035). The increase in risk of mite sensitization with increasing Der p 1 exposure was consistently higher among children with filaggrin mutations, but the interaction did not reach statistical significance. Different association were observed for dog: there was a significant interaction between filaggrin and dog ownership, but the risk of sensitization to any allergen was significantly lower among children with filaggrin mutations who were exposed to dog in infancy (OR 0.16, 95% CI 0.03–0.86, p=0.03).
Conclusions
Filaggrin loss-of function mutations modify the relationship between allergen exposure and sensitization, but effects differ at different ages and between different allergens.
Date Issued
2020-03
Date Acceptance
2019-08-21
Citation
Journal of Allergy and Clinical Immunology, 2020, 145 (3), pp.993-1001
ISSN
0091-6749
Publisher
Elsevier BV
Start Page
993
End Page
1001
Journal / Book Title
Journal of Allergy and Clinical Immunology
Volume
145
Issue
3
Copyright Statement
©2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy ofAllergy, Asthma & Immunology. This is an open access article under the CC BY li-cense (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Medical Research Council (MRC)
Identifier
https://www.sciencedirect.com/science/article/pii/S0091674919313235?via%3Dihub
Grant Number
MR/K002449/1
Subjects
Allergen exposure
Can f 1
Der p 1
Fel d 1
birth cohort
cat
childhood
dog
filaggrin
house dust mite
sensitization
Allergy
1107 Immunology
Publication Status
Published
Date Publish Online
2019-10-17