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

被引：2

作者：

Martino, David ^{[1
,2
]}

Kresoje, Nina ^{[1
]}

Amenyogbe, Nelly ^{[1
,3
]}

Ben-Othman, Rym ^{[4
]}

Cai, Bing ^{[5
]}

Lo, Mandy ^{[5
]}

Idoko, Olubukola ^{[6
]}

Odumade, Oludare A. ^{[7
,8
]}

Falsafi, Reza ^{[9
]}

Blimkie, Travis M. ^{[9
]}

An, Andy ^{[9
]}

Shannon, Casey P. ^{[10
,11
]}

Montante, Sebastiano ^{[12
]}

Dhillon, Bhavjinder K. ^{[9
]}

Diray-Arce, Joann ^{[7
,8
]}

Al Ozonoff, Al

Smolen, Kinga K. ^{[7
,8
]}

Brinkman, Ryan R. ^{[12
]}

Mcenaney, Kerry ^{[7
]}

Angelidou, Asimenia ^{[7
,8
,14
]}

Richmond, Peter ^{[1
,2
]}

Tebbutt, Scott J. ^{[10
,11
,15
]}

EPIC HIPC consortium, Beate

Kampmann, Beate ^{[6
,16
,17
]}

Levy, Ofer ^{[7
,8
,13
]}

Hancock, Robert E. W. ^{[9
]}

Lee, Amy H. Y. ^{[18
]}

Kollmann, Tobias R. ^{[1
,3
]}

机构：

[1] Univ Western Australia, Perth, WA, Australia

[2] Univ Western Australia, Crawley, WA 6009, Australia

[3] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS, Canada

[4] RAN BioLinks Ltd, 10212 Yonge St 202, Richmond Hill, ON L4C 3B6, Canada

[5] Univ British Columbia, BC Childrens Hosp, Vancouver, BC, Canada

[6] London Sch Hyg & Trop Med, Med Res Council Unit Gambia, Vaccines & Immun Theme, Atlantic Blvd, Banjul, Gambia

[7] Boston Childrens Hosp, Dept Pediat, Precis Vaccines Program, Boston, MA 02115 USA

[8] Harvard Med Sch, Boston, MA USA

[9] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC, Canada

[10] PROOF Ctr Excellence, Vancouver, BC, Canada

[11] St Pauls Hosp, UBC Ctr Heart Lung Innovat, Vancouver, BC, Canada

[12] BC Canc Agcy, Vancouver, BC, Canada

[13] Broad Inst MIT & Harvard, Cambridge, MA USA

[14] Beth Israel Deaconess Med Ctr, Dept Neonatol, Boston, MA USA

[15] Univ British Columbia, Dept Med, Div Resp Med, Vancouver, BC, Canada

[16] Charite, Ctr Global Hlth, Berlin, Germany

[17] Charite, Inst Int Hlth, Berlin, Germany

[18] Simon Fraser Univ, Mol Biol & Biochem, Burnaby, BC, Canada

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

TO-LYMPHOCYTE; GLOBAL BURDEN; NEWBORN; SUSCEPTIBILITY; IDENTIFICATION; COUNTRIES; IMMUNITY; REVEALS; PACKAGE; DISEASE;

D O I：

10.1038/s41467-024-52283-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 54 条

[1] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[2] Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays [J].

Aryee, Martin J. ;

Jaffe, Andrew E. ;

Corrada-Bravo, Hector ;

Ladd-Acosta, Christine ;

Feinberg, Andrew P. ;

Hansen, Kasper D. ;

Irizarry, Rafael A. .

BIOINFORMATICS, 2014, 30 (10) :1363-1369

[3] Alterations in Immune-Related Defensin Alpha 4 (DEFA4) Gene Expression in Health and Disease [J].

Basingab, Fatemah ;

Alsaiary, Abeer ;

Almontashri, Shahad ;

Alrofaidi, Aisha ;

Alharbi, Mona ;

Azhari, Sheren ;

Algothmi, Khloud ;

Alhazmi, Safiah .

INTERNATIONAL JOURNAL OF INFLAMMATION, 2022, 2022

[4] Epigenetic regulation of pediatric and neonatal immune responses [J].

Bermick, Jennifer ;

Schaller, Matthew .

PEDIATRIC RESEARCH, 2022, 91 (02) :297-327

[5] Newborn susceptibility to infection vs. disease depends on complex in vivo interactions of host and pathogen [J].

Brook, Byron ;

Harbeson, Danny ;

Ben-Othman, Rym ;

Viemann, Dorothee ;

Kollmann, Tobias R. .

SEMINARS IN IMMUNOPATHOLOGY, 2017, 39 (06) :615-625

[6] LD Score regression distinguishes confounding from polygenicity in genome-wide association studies [J].

Bulik-Sullivan, Brendan K. ;

Loh, Po-Ru ;

Finucane, Hilary K. ;

Ripke, Stephan ;

Yang, Jian ;

Patterson, Nick ;

Daly, Mark J. ;

Price, Alkes L. ;

Neale, Benjamin M. .

NATURE GENETICS, 2015, 47 (03) :291-+

[7] Second-generation PLINK: rising to the challenge of larger and richer datasets [J].

Chang, Christopher C. ;

Chow, Carson C. ;

Tellier, Laurent C. A. M. ;

Vattikuti, Shashaank ;

Purcell, Shaun M. ;

Lee, James J. .

GIGASCIENCE, 2015, 4

[8] Lymphotoxin-α gene and risk of myocardial infarction in 6,928 cases and 2,712 controls in the ISIS case-control study [J].

Clarke, Robert ;

Xu, Peng ;

Bennett, Derrick ;

Lewington, Sarah ;

Zondervan, Krina ;

Parish, Sarah ;

Palmer, Alison ;

Clark, Sarah ;

Cardon, Lon ;

Peto, Richard ;

Lathrop, Mark ;

Collins, Rory .

PLOS GENETICS, 2006, 2 (07) :990-996

[9] Why are preterm newborns at increased risk of infection? [J].

Collins, Amelie ;

Weitkamp, Jorn-Hendrik ;

Wynn, James L. .

ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, 2018, 103 (04) :F391-F394

[10] Clinical research in neonates and infants: Challenges and perspectives [J].

Coppini, Raffaele ;

Simons, Sinno H. P. ;

Mugelli, Alessandro ;

Allegaert, Karel .

PHARMACOLOGICAL RESEARCH, 2016, 108 :80-87

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