Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion

Anna R. Smith, Department of Epidemiology and Population Health, Stanford Medicine, Stanford, CA, USA.
Pi-I D. Lin, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Sheryl L. Rifas-Shiman, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Abby F. Fleisch, Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Westbrook, ME, USA; Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland, ME, USA.
Robert O. Wright, Department of Environmental Medicine and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Brent Coull, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Patricia W. Finn, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Emily Oken, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Diane R. Gold, Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Andres Cardenas, Department of Epidemiology and Population Health, Stanford Medicine, Stanford, CA, USA. Electronic address: andresca@stanford.edu.

Document Type

Article

Publication Date

7-3-2024

Institution/Department

CORE; Pediatrics

Journal Title

Environmental research

Abstract

BACKGROUND: Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response. OBJECTIVE: We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion. METHODS: We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269-314) and cytokine secretion (n = 217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers. RESULTS: Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively. CONCLUSIONS: Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood.

First Page

119555

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