title: Peanut allergy: effect of environmental peanut exposure in children with filaggrin loss-of-function mutations.
abstract: 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.
  
  
  
  We sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology, King's College London and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Brough
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
authors.affiliation: Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology, King's College London and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Kerry
authors.initials: K
authors.lastname: Makinson
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Jenny
authors.initials: J
authors.lastname: Hankinson
authors.affiliation: Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Brown
authors.affiliation: Department of Public Health Science, School of Medicine, King's College London, London, United Kingdom.
authors.forename: Abdel
authors.initials: A
authors.lastname: Douiri
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom; Centre for Dermatology and Genetic Medicine, College of Life Sciences and College of Medicine, Dentistry and Nursing, University of Dundee, Dundee, United Kingdom.
authors.forename: Danielle C M
authors.initials: DC
authors.lastname: Belgrave
authors.affiliation: Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology, King's College London and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Penagos
authors.affiliation: Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology, King's College London and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Alick C
authors.initials: AC
authors.lastname: Stephens
authors.affiliation: Centre for Health Informatics, Institute of Population Health, University of Manchester, Manchester, United Kingdom.
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.affiliation: Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology, King's College London and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Victor
authors.initials: V
authors.lastname: Turcanu
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Nicolaou
authors.affiliation: Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre, University of Manchester and University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Adnan
authors.initials: A
authors.lastname: Custovic
authors.affiliation: Department of Pediatric Allergy, Division of Asthma, Allergy and Lung Biology, King's College London and Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom. Electronic address: Gideon.lack@kcl.ac.uk.
authors.forename: Gideon
authors.initials: G
authors.lastname: Lack
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D010367:Arachis / Q000737:chemistry / Q000276:immunology*; D002648:Child; D015331:Cohort Studies; D004391:Dust / Q000032:analysis*; D004781:Environmental Exposure / Q000009:adverse effects; D000091344:Filaggrin Proteins; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D021183:Peanut Hypersensitivity / Q000235:genetics / Q000276:immunology*; D012306:Risk
chemical_list: D000485:Allergens; D004391:Dust; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins
keywords: FLG loss-of-function mutations; dust; environmental peanut exposure; filaggrin; peanut allergy; peanut sensitization; skin barrier; threshold