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Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA

David Martino1, Nikki Schultz2, Ravinder Kaur3

  • 1Wal-Yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia. david.martino@telethonkids.org.au.

Clinical Epigenetics
|July 3, 2024
PubMed

Insights

Infants with frequent respiratory infections show impaired immunity and are prone to asthma. Epigenetic profiling identified molecular pathways for early identification and potential immune modulation in these children.

Area of Science:

  • Immunology
  • Epigenetics
  • Pediatrics

Background:

  • Infants with frequent respiratory infections have compromised immunity and increased risk of chronic respiratory diseases.
  • These infants are more prone to low vaccine responsiveness (LVR).

Purpose of the Study:

  • Investigate epigenetic profiling for endotype-specific molecular pathways in infants.
  • Explore potential for early identification and immuno-modulation in infection allergy/asthma-prone (IAP) infants.

Main Methods:

  • Retrospective analysis of peripheral blood mononuclear cells from IAP and non-infection allergy/asthma-prone (NIAP) infants.
  • Genome-wide DNA methylation and single nucleotide polymorphism analysis were performed.
  • Mononuclear cells were stimulated with monophosphoryl lipid A (MPL), a TLR agonist.

Main Results:

  • Identified an endotype signature of 813 differentially methylated regions (DMRs) linked to asthma, mucin production, antigen presentation, and inflammasome activation.
  • Allelic variation had a minimal impact on the identified epigenetic signature.
  • MPL stimulation partially reversed the epigenetic signature, indicating potential for remodeling.

Conclusions:

  • This study provides a foundation for precision endotyping of IAP children.
  • Highlights the potential of immune modulation strategies using adjuvants for future research.
Abstract

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