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

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, Sebastiano Montante, Bhavjinder K. Dhillon, Joann Diray-Arce, Al Ozonoff, Kinga K. Smolen, Ryan R. Brinkman, Kerry McEnaney, Asimenia Angelidou, Peter Richmond, Scott J. Tebbutt, Beate Kampmann, Ofer Levy, Robert E. W. Hancock, Amy H. Y. Lee and Tobias R. Kollmann
Additional contact information
David Martino: The Kids Research Institute Australia
Nina Kresoje: The Kids Research Institute Australia
Nelly Amenyogbe: The Kids Research Institute Australia
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
Reza Falsafi: University of British Columbia
Travis M. Blimkie: University of British Columbia
Andy An: University of British Columbia
Casey P. Shannon: Providence Research
Sebastiano Montante: BC Cancer Agency
Bhavjinder K. Dhillon: University of British Columbia
Joann Diray-Arce: Boston Children’s Hospital
Al Ozonoff: Boston Children’s Hospital
Kinga K. Smolen: Boston Children’s Hospital
Ryan R. Brinkman: BC Cancer Agency
Kerry McEnaney: Boston Children’s Hospital
Asimenia Angelidou: Boston Children’s Hospital
Peter Richmond: The Kids Research Institute Australia
Scott J. Tebbutt: Providence Research
Beate Kampmann: Atlantic Boulevard
Ofer Levy: Boston Children’s Hospital
Robert E. W. Hancock: University of British Columbia
Amy H. Y. Lee: Simon Fraser University
Tobias R. Kollmann: The Kids Research Institute Australia

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52283-9

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