Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma

J Allergy Clin Immunol. 2020 Oct;146(4):821-830. doi: 10.1016/j.jaci.2020.02.031. Epub 2020 Mar 15.

Abstract

Background: Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines.

Objective: We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma.

Methods: IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease. We applied clustering methods to identify co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma.

Results: Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school children and adults with mild/moderate compared with those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups.

Conclusions: The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity among school children and adults with allergic asthma.

Keywords: Asthma; allergic sensitization; cluster; network analysis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Allergens / immunology*
  • Antibody Specificity / immunology*
  • Asthma / diagnosis*
  • Asthma / immunology*
  • Biomarkers
  • Body Mass Index
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Europe
  • Female
  • Humans
  • Immunization
  • Immunoglobulin E / immunology*
  • Male
  • Middle Aged
  • Prognosis
  • Severity of Illness Index
  • Young Adult

Substances

  • Allergens
  • Biomarkers
  • Immunoglobulin E