Peanut allergy: Effect of environmental peanut exposure in children with filaggrin loss-of-function mutations - 02/10/14
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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.
Le texte complet de cet article est disponible en PDF.Key words : FLG loss-of-function mutations, filaggrin, skin barrier, peanut sensitization, peanut allergy, environmental peanut exposure, dust, threshold
Abbreviations used : AD, CRD, FLG, GEE, ISU, LLQ, MAAS, OFC, OR, sIgE, SPT
Plan
The research was funded by Action Medical Research (S/P/4529) and supported by the National Institute for Health Research (NIHR) Clinical Research Facility at Guy's & St Thomas' NHS Foundation Trust and the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and Kings College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Manchester Asthma and Allergy Study is supported by Medical Research Council grants G0601361 and MR/K002449/1, the JP Moulton Charitable Foundation, North West Lung Centre Charity, and the National Institute for Health Research Clinical Research Facility at the University Hospital of South Manchester NHS Foundation Trust. The Centre for Dermatology and Genetic Medicine, University of Dundee, is funded by a Wellcome Trust Strategic Award (098439/Z/12/Z; to W.H.I.M.). S.B. holds a Wellcome Intermediate Clinical Fellowship (086398/Z/08/Z). |
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Disclosure of potential conflict of interest: H. A. Brough has received research support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust and Action Medical Research, UK. A. Simpson has received research support from the Medical Research Council, JP Moulton Charitable Foundation, and the National Institute of Health Research. K. Makinson has received research support from the Department of Health through the National Institute of Health Research comprehensive Biomedical Research Centre award to Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust and the Immune Tolerance Network, National Institutes of Health. S. Brown has received research support from the Wellcome Trust Intermediate Clinical Fellowship and has received payment for lectures from the American Academy of Allergy, Asthma & Immunology. A. Douiri has received research support from the National Institute of Health Research. A. C. Stephens has received research support from the Department of Health through the NIHR comprehensive Biomedical Research Centre award to Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. W. H. I. McLean has received research support from the Wellcome Trust. A. Custovic has consultant arrangements with Circassia; has received research support from the Medical Research Council and the Moulton Charitable Foundation; and has received payment for lectures from GlaxoSmithKline, Thermo Fisher Scientific, Novartis, and ALK-Abelló. G. Lack has received research support from the Department of Health through the NIHR comprehensive Biomedical Research Centre award to Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust and Action Medical Research, UK; is a board member of DBV Technologies; has consultant arrangements with the Anaphylaxis Campaign and the National Peanut Board; has received payment for lectures from Sodilac, Novartis, Nestle Nutrition, GlaxoSmithKline, and the Serono Symposia International Foundation; and has stock/stock options with DBV Technologies. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 134 - N° 4
P. 867 - octobre 2014 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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