title: Allergen-specific IgG antibody levels modify the relationship between allergen-specific IgE and wheezing in childhood.
abstract: BACKGROUND
  An increase in IgE antibody levels to inhalant allergens is associated with an increased likelihood of wheezing. The role of allergen-specific IgG and IgG4 in relation to wheezing is yet to be determined.
  
  
  OBJECTIVE
  We sought to investigate whether Fel d 1-specific IgG and IgG4 antibodies modify the association between cat allergen-specific IgE and childhood wheezing.
  
  
  METHODS
  We used data from 2 population-based birth cohorts (United Kingdom [UK], n = 473; Australia, n = 1336). Current wheeze was defined as wheezing in the previous 12 months at age 5 (UK) and 14 (Australia) years. We determined cat allergen-specific IgE (whole extract) and IgG and IgG4 antibody (purified rFel d 1) levels and used logistic regression to estimate the relationship between wheeze and the quantitative allergen antibody levels.
  
  
  RESULTS
  In the univariate analysis risk of wheezing increased significantly with increasing cat-specific IgE levels (UK: odds ratio [OR], 1.56; 95% CI, 1.28-1.90; Australia: OR, 1.29; 95% CI, 1.19-1.40). rFel d 1-specific IgG or IgG4 had no significant effect on wheeze in either population. However, a different pattern of the relationship between antibody levels and wheezing emerged in the multivariate analysis. In the UK cat-specific IgE increased the risk of wheeze (OR, 2.01; 95% CI, 1.29-3.12; P = .002), whereas rFel d 1-specific IgG decreased the risk (OR, 0.46; 95% CI, 0.21-0.99; P = .05). This finding was replicated in Australia (IgE: OR, 1.46; 95% CI, 1.28-1.68; P < .001; IgG: OR, 0.66; 95% CI, 0.44-0.99; P = .049). There was no significant association between IgG4 antibody levels and wheezing in either population.
  
  
  CONCLUSIONS
  rFel d 1-specific IgG but not IgG4 antibody levels significantly modify the association between cat-specific IgE and childhood wheezing, with the risk of symptoms decreasing with increasing IgG levels.
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom. adnan.custovic@manchester.ac.uk
authors.forename: Adnan
authors.initials: A
authors.lastname: Custovic
authors.forename: Lars
authors.initials: L
authors.lastname: Soderstrom
authors.forename: Staffan
authors.initials: S
authors.lastname: Ahlstedt
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Angela
authors.initials: A
authors.lastname: Simpson
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000293:Adolescent; D000485:Allergens; D000818:Animals; D000918:Antibody Specificity; D001249:Asthma / Q000209:etiology / Q000276:immunology; D002415:Cats; D002675:Child, Preschool; D015331:Cohort Studies; D004739:England; D006023:Glycoproteins; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D015999:Multivariate Analysis; D012135:Respiratory Sounds / Q000276:immunology*; D012307:Risk Factors; D014904:Western Australia
chemical_list: D000485:Allergens; D006023:Glycoproteins; D007074:Immunoglobulin G; D007073:Immunoglobulin E; C059296:Fel d 1 protein, Felis domesticus