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Distinct immune phenotypes in infants developing asthma during childhood

Anna Hammerich Thysen1,2, Johannes Waage1, Jeppe Madura Larsen2

  • 1COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, DK-2200 Copenhagen, Denmark.

Science Translational Medicine
|February 7, 2020
PubMed

Insights

Infant immune responses predict childhood asthma. Early abnormal neutrophil antiviral responses linked to transient asthma, while enhanced IL-5/IL-13 production and bacterial colonization predicted persistent asthma.

Area of Science:

  • Immunology
  • Pediatrics
  • Environmental Health

Background:

  • Early life immune responses are crucial for development and disease susceptibility.
  • Childhood asthma is a complex condition with diverse underlying immune mechanisms.
  • Environmental factors interact with host immunity to influence disease trajectories.

Purpose of the Study:

  • To investigate the relationship between early immune competence in infants and the development of transient or persistent childhood asthma.
  • To identify specific immune response phenotypes at 18 months of age that predict asthma development by 6 years of age.
  • To explore the role of early life bacterial colonization in mediating immune responses linked to asthma.

Main Methods:

  • Functional immune profiling of 186 parameters in blood samples from 541 infants at 18 months of age.
  • Assessment of asthma development (transient or persistent) at 6 years of age.
  • Analysis of associations between infant immune response phenotypes, including T cell cytokine production (IL-5, IL-13) and neutrophil responses, and early life airway bacterial colonization.

Main Results:

  • An abnormal neutrophil-linked antiviral response in infants was associated with an increased risk of developing transient asthma.
  • Infants who later developed persistent asthma exhibited enhanced production of interleukin-5 (IL-5) and interleukin-13 (IL-13) from stimulated T cells at 18 months.
  • This enhanced IL-5 and IL-13 production was linked to early life bacterial colonization of the airways.
  • Distinct early immune characteristics were identified in infants who developed different asthma endotypes.

Conclusions:

  • Early immune profiling can identify infants at risk for specific asthma endotypes.
  • Neutrophil antiviral responses and T cell cytokine profiles (IL-5, IL-13) in infancy are early indicators of asthma trajectories.
  • Early life bacterial colonization may play a role in shaping immune responses that lead to persistent asthma.

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