Allergen-specific IgG antibody levels modify the relationship between allergen-specific IgE and wheezing in childhood

BackgroundAn 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.ObjectiveWe sought to investigate whether Fel d 1–specific IgG and IgG4 antibodies modify the association between cat allergen–specific IgE and childhood wheezing.MethodsWe 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.ResultsIn 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.ConclusionsrFel 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.