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DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life

Author

Listed:
  • David Martino

    (The Kids Research Institute Australia
    University of Western Australia)

  • Nina Kresoje

    (The Kids Research Institute Australia)

  • Nelly Amenyogbe

    (The Kids Research Institute Australia
    Dalhousie University)

  • Rym Ben-Othman

    (RAN BioLinks Ltd)

  • Bing Cai

    (University of British Columbia)

  • Mandy Lo

    (University of British Columbia)

  • Olubukola Idoko

    (Atlantic Boulevard)

  • Oludare A. Odumade

    (Boston Children’s Hospital
    Harvard Medical School)

  • Reza Falsafi

    (University of British Columbia)

  • Travis M. Blimkie

    (University of British Columbia)

  • Andy An

    (University of British Columbia)

  • Casey P. Shannon

    (Providence Research
    St. Paul’s Hospital)

  • Sebastiano Montante

    (BC Cancer Agency)

  • Bhavjinder K. Dhillon

    (University of British Columbia)

  • Joann Diray-Arce

    (Boston Children’s Hospital
    Harvard Medical School)

  • Al Ozonoff

    (Boston Children’s Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Kinga K. Smolen

    (Boston Children’s Hospital
    Harvard Medical School)

  • Ryan R. Brinkman

    (BC Cancer Agency)

  • Kerry McEnaney

    (Boston Children’s Hospital)

  • Asimenia Angelidou

    (Boston Children’s Hospital
    Harvard Medical School
    Beth Israel Deaconess Medical Centre)

  • Peter Richmond

    (The Kids Research Institute Australia
    University of Western Australia)

  • Scott J. Tebbutt

    (Providence Research
    St. Paul’s Hospital
    University of British Columbia)

  • Beate Kampmann

    (Atlantic Boulevard
    Charite Universitatsmedizin)

  • Ofer Levy

    (Boston Children’s Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Robert E. W. Hancock

    (University of British Columbia)

  • Amy H. Y. Lee

    (Simon Fraser University)

  • Tobias R. Kollmann

    (The Kids Research Institute Australia
    Dalhousie University)

Abstract

Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood samples collected from West African neonates on days of life (DOL) 0, 1, 3, and 7. Genome-wide DNA methylation and single nucleotide polymorphism markers are examined alongside matched transcriptomic and flow cytometric data. Integrative analysis reveals that a core network of transcription factors mediates dynamic shifts in neutrophil-to-lymphocyte ratios (NLR), which are underpinned by cell-type specific methylation patterns in the two cell types. Genetic variants are associated with lower NLRs at birth, and healthy newborns with lower NLRs at birth are more likely to subsequently develop sepsis. These findings provide valuable insights into the early-life determinants of immune system development.

Suggested Citation

  • David Martino & Nina Kresoje & Nelly Amenyogbe & Rym Ben-Othman & Bing Cai & Mandy Lo & Olubukola Idoko & Oludare A. Odumade & Reza Falsafi & Travis M. Blimkie & Andy An & Casey P. Shannon & Sebastian, 2024. "DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52283-9
    DOI: 10.1038/s41467-024-52283-9
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    References listed on IDEAS

    as
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