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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:145

Article

Simpson, Angela^1,2  Brough, Helen A.^3,4,5  Haider, Sadia^6,7  Belgrave, Danielle⁷  Murray, Clare S.^1,2  Custovic, Adnan^6,7 

[1] Univ Manchester, Div Infect Immun & Resp Med, Fac Biol Med & Hlth, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[2] Univ Hosp South Manchester NHS Fdn Trust, Manchester, Lancs, England

[3] Guys & St Thomas NHS Trust, Childrens Allergy Serv, Evelina London, London, England

[4] Sch Life Course Sci, Paediat Allergy Grp, Dept Women & Childrens Heath, London, England

[5] Kings Coll London, Paediat Allergy Grp, Sch Immunol & Microbial Sci, London, England

[6] Imperial Coll London, Sect Paediat, London, England

[7] Microsoft Res Cambridge, Cambridge, England

关键词: Allergen exposure;    house dust mite;    cat;    dog;    sensitization;    birth cohort;    filaggrin;    childhood;    Fel d 1;    Der p 1;    Can f 1;   

DOI  :  10.1016/j.jaci.2019.08.041

来源: Elsevier

【 摘 要 】

Background: We hypothesized that filaggrin (FLG) loss-of-function mutations modify the effect of allergen exposure on the development of allergic sensitization. Objective: We sought to determine whether early-life exposure to inhalant allergens increases the risk of specific sensitization and whether FLG 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 6 FLG mutations. Results: 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). Conclusions: FLG loss-of-function mutations modify the relationship between allergen exposure and sensitization, but effects differ at different ages and between different allergens.

【 授权许可】

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