Biological sex impacts immune cell proportions and epigenetic profiles in the developing pediatric immune system

Biological sex impacts immune cell proportions and epigenetic profiles in the developing pediatric immune system | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Biological sex impacts immune cell proportions and epigenetic profiles in the developing pediatric immune system Michael Kobor, Karlie Edwards, Sarah Merrill, Chaini Konwar, Marcia Jude, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5141819/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Oct, 2025 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract Age- and sex-related differences in immune cell compositions and immune outcomes have been identified in adult and aging populations, but a comprehensive and nuanced characterization of these changes during the rapid developmental window of early life is lacking. We explored the association with sex and age within the immune system in CHILD, a Canadian longitudinal pediatric cohort, leveraging DNA methylation (DNAm) from whole blood samples collected at ages one and five years (n=760 paired, 356 female and 404 male). Using DNAm-based computational cell type deconvolution, we observed changes in all twelve estimated immune cell type proportions between these ages in a pediatric population and found significant differences in the context of biological sex. We also identified distinct age- and sex-specific DNAm signatures in the immune system in the first five years of life. Notably, there were few age-specific DNAm changes and the sex-specific DNAm were consistent across this early life developmental window. We were then able to validate many of the sex-specific DNAm changes in separate pediatric cohorts. This insight not only enhances our understanding of pediatric immune maturation and system composition in a healthy population but highlights the existence of sex-based differences prior to puberty. Biological sciences/Immunology/Immunogenetics Biological sciences/Genetics/Epigenetics/DNA methylation Immune system DNAm early life DOHaD Sex differences Full Text Additional Declarations There is NO Competing Interest. Supplementary Files CommunicationsBiologySupplementalFiguresKE.pdf CommunicationsBiologySupplementalTablesKE.xlsx Cite Share Download PDF Status: Published Journal Publication published 09 Oct, 2025 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5141819","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":365029403,"identity":"5e0b5198-d1f5-4fa7-b4b6-c2f5e62460b3","order_by":0,"name":"Michael 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