Growth curves of “normal” serum total IgE levels throughout childhood: A quantile analysis in a birth cohort
Authors: Sacco Chiara , Perna Serena , Vicari Donatella , Alfò Marco , Bauer Carl‐Peter , Hoffman Ute , Forster Johannes , Zepp Fred , Schuster Antje , Wahn Ulrich , Keil Thomas , Lau Susanne , Matricardi Paolo Maria 
Published: May 2017

Background

Previous studies of serum total IgE (t‐IgE) were not able to discriminate well‐enough atopic from non‐atopic subjects, that is, 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 20 years. Total and specific IgE (t‐IgE, s‐IgE) were analyzed 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 (cutoff: <0.35 kUA/L) for s‐IgE to the nine 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 5 years, 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 cutoff 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 5 years of age, increased to a plateau at age 10‐13 years, and decreased slightly afterward. 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.

Conclusion

The growth curves of “normal” serum t‐IgE concentrations were estimated in “never atopic” children; for each individual who was non‐atopic at 5 years 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 6 to 20 years of age, predicted at each year the occurrence of atopic sensitization.

Clinical Implications

The trajectory of t‐IgE levels can be elaborated since age 5 years in non‐atopic children. A child whose t‐IgE levels are consistently higher than those predicted by his/her growth curve may have developed atopic sensitization.