Growth curves of "normal" serum total IgE levels throughout childhood: a quantile analysis in a birth cohort

Background Previous studies of serum total IgE (t-IgE) were not able to discriminate well enough atopic from non-atopic subjects, i.e. with or without serum-specific IgE antibodies to allergens. Objectives To model growth curves of the total IgE levels in children without atopic sensitization (hereafter defined as “normal” t-IgE levels) and to test their usefulness in predicting atopic sensitization. Methods The German Multicentre Allergy Study (MAS), a birth cohort with 1314 recruited newborns, began in 1990 and examined the participants until age 20y. Total and specific IgE (t-IgE, s-IgE) were analysed with a fluorescent enzyme immunoassay ImmunoCAP (TFS, Sweden) at ages 1,2,3,5,6,7,10,13 and 20 years. Participants were classified as “never atopic” if all their available serum samples had negative response (cut-off: <0.35 kUA/l) for s-IgE to the 9 common foodborne and airborne allergenic extracts (milk, egg, soy, wheat, house dust mite, cat, dog, birch and grass) tested in the MAS birth cohort. By contrast, participants were defined as atopic if they had , for at least at one available serum sample, s-IgE ≥ 0.35 kUA/l to at least one allergenic extract tested. The evolution of t-IgE levels in the “never atopic” children was described by growth curves, estimated by exploiting a quantile regression model. A “reference” percentile, based on the t-IgE value measured at age 5y, was assigned to each child with no IgE sensitization at that age. Upward deviations from the own “reference” quantile of t-IgE in atopic and “never atopic” children were calculated and a ROC analysis was used to identify the best cut-off point for predicting atopic sensitization. Results Overall, 1113 of 1314 children were included in this analysis. Of these, 469 were “never atopic” and 644 atopic. Quantile trajectories of t-IgE levels in “never atopic” subjects were stable from 5y of age, increased to a plateau at age 10-13y, and decreased slightly afterwards. The onset of atopic s-IgE responses was characterized by an upward deviation of serum t-IgE levels from their “reference” trajectory. T-IgE quantiles predicted the onset of atopy with high efficiency (AUC >80%). ROC analysis showed that deviations from the t-IgE level “reference” quantile above 0.32, 0.41, 0.42, 0.30 and 0.58 kU/l (log-units) at 6,7,10,13 and 20 years of age, respectively, predicted an atopic sensitization. Conclusions The growth curves of “normal” serum t-IgE concentrations were estimated in “never atopic” children; for each individual who was non-atopic at 5ys of age a “reference” quantile was identified that represented the individual's “normal” level of t-IgE production. Upward deviations of observed t-IgE levels from the own “reference” quantile, from 6ys to 20ys of age, predicted at each year the occurrence of atopic sensitization.