TY - JOUR
T1 - DNA Methylation signatures underpinning blood neutrophil to lymphocyte ratio during first week of human life
AU - the EPIC-HIPC consortium
AU - Martino, David
AU - Kresoje, Nina
AU - Amenyogbe, Nelly
AU - Ben-Othman, Rym
AU - Cai, Bing
AU - Lo, Mandy
AU - Idoko, Olubukola
AU - Odumade, Oludare A.
AU - Falsafi, Reza
AU - Blimkie, Travis M.
AU - An, Andy
AU - Shannon, Casey P.
AU - Montante, Sebastiano
AU - Dhillon, Bhavjinder K.
AU - Diray-Arce, Joann
AU - Ozonoff, Al
AU - Smolen, Kinga K.
AU - Brinkman, Ryan R.
AU - McEnaney, Kerry
AU - Angelidou, Asimenia
AU - Richmond, Peter
AU - Tebbutt, Scott J.
AU - Kampmann, Beate
AU - Levy, Ofer
AU - Hancock, Robert E.W.
AU - Lee, Amy H.Y.
AU - Kollmann, Tobias R.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85204452773&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-52283-9
DO - 10.1038/s41467-024-52283-9
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C2 - 39289350
AN - SCOPUS:85204452773
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 8167
ER -