Cytokine responses to rhinovirus and development of asthma, allergic sensitization and respiratory infections during childhood

Research output: Contribution to journalArticle

  • External authors:
  • Adnan Custovic
  • Danielle Belgrave
  • Lijing Lin
  • Eteri Bakhsoliani
  • Aurica G. Telcian
  • Roberto Solari
  • Ross P. Walton
  • Michael R Edwards
  • Sebastian L. Johnston

Abstract

Background: Immunophenotypes of anti-viral responses, and their relationship with asthma, allergy and lower respiratory tract infections (LRTIs) are poorly understood. We characterized multiple cytokine responses of peripheral-blood mononuclear cells to rhinovirus stimulation, and their relationship with clinical outcomes. Methods: In a population-based birth cohort, we measured 28 cytokines post-stimulation with rhinovirus-16 in 307 children aged 11 years. We used machine learning to identify patterns of cytokine responses, and related these patterns to clinical outcomes using longitudinal models. We also ascertained phytohaemagglutinin-induced TH2-cytokine responses [PHA-TH2]. Results: We identified six clusters of children based on their rhinovirus-16 responses, which were differentiated by the expression of four cytokine/chemokine groups: interferon-related-(IFN); pro-inflammatory-(Inflam); TH2-chemokine-(TH2-chem); regulatory-(Reg). Clusters differed in their clinical characteristics. Children with IFNmodInflamhighestTH2-chemhighestReghighest rhinovirus-16-induced pattern had PHA-TH2low response, and a very low asthma risk (OR:0.08 [95%CI 0.01–0.81], P=0.03). Two clusters had high risk of asthma and allergic sensitization, but with different trajectories from infancy to adolescence. The IFNlowestInflamhighTH2-chemlowRegmod cluster exhibited PHA-TH2lowest response, and was associated with early-onset asthma and sensitization, and the highest risk of asthma exacerbations (1.37 [1.07–1.76], P=0.014) and LRTI hospitalizations (2.40 [1.26–4.58], P=0.008) throughout childhood. In contrast, cluster with IFNhighestInflammodTH2-chemmodReghigh rhinovirus-16-cytokine pattern was characterized by PHA-TH2highest response, and a low prevalence of asthma/sensitization in infancy which increased sharply to become the highest among all clusters by adolescence (but with low risk of asthma exacerbations). Conclusions: Early-onset troublesome asthma with early-life sensitization, later-onset milder allergic asthma, and disease protection are each associated with different patterns of rhinovirus-induced immune responses.

Bibliographical metadata

Original languageEnglish
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume197
Issue number10
Early online date21 Feb 2018
DOIs
StatePublished - 15 May 2018