{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T18:47:35Z","timestamp":1773341255681,"version":"3.50.1"},"posted":{"date-parts":[[2024,11,18]]},"group-title":"Allergy and Immunology","reference-count":109,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Environmental exposures to chemical toxicants during gestation and infancy can dysregulate multiple developmental processes, causing lifelong effects. There is compelling evidence of PFAS-associated immunotoxicity in adults and children. However, the effect of developmental PFAS exposure on infant T-cell immunity is unreported, and, if present, could be implicated in immune-related health outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We seek to model longitudinal changes in CD4+ T-cell subpopulations from birth through 12 months and their association with in-utero PFAS exposure and postnatal CD4+ T-cell frequencies and functions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant\u2019s first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, and PFHXS) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n=200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and pre-pregnancy body mass index.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    In-utero PFAS exposure correlated with multiple CD4+ T-cell subpopulations in infants. The greatest effect sizes were seen in T-follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months. A log\n                    <jats:sub>2<\/jats:sub>\n                    -unit increase in PFOS was associated with lower Tfh [0.17% (95%CI: \u22120.30, \u22120.40)] and greater Th2 [0.27% (95%CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, and PFHXS.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated, protective immunity. Future studies into the role of PFAS-associated T-cell distribution and risk of adverse immune-related health outcomes in children are warranted.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.11.18.24317489","type":"posted-content","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T22:05:10Z","timestamp":1731967510000},"source":"Crossref","is-referenced-by-count":1,"title":["In utero exposure to per \u2013 and polyfluoroalkyl substances (PFAS) associates with altered human infant T helper cell development"],"prefix":"10.64898","author":[{"given":"Darline Castro","family":"Mel\u00e9ndez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Laniewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd 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Lawrence","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zorimar","family":"Rivera-N\u00fa\u00f1ez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meghan","family":"Best","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison","family":"Macomber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Leger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurunthachalam","family":"Kannan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard 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