Associations between per- and poly-fluoroalkyl substance (PFAS) exposure and immune responses among women in the California Teachers study: A cross-sectional evaluation

Emily L Cauble; Peggy Reynolds; Marta Epeldegui; Syam S Andra; Larry Magpantay; Srinivasan Narasimhan; Divya Pulivarthi; Julie Von Behren; Otoniel Martinez-Maza; Debbie Goldberg; Emma S Spielfogel; James V Lacey Jr; Sophia S Wang

doi:10.1016/j.cyto.2024.156753

Associations between per- and poly-fluoroalkyl substance (PFAS) exposure and immune responses among women in the California Teachers study: A cross-sectional evaluation

Cytokine. 2024 Sep 18:184:156753. doi: 10.1016/j.cyto.2024.156753. Online ahead of print.

Affiliations

¹ Division of Health Analytics, Beckman Research Institute, City of Hope, Duarte, CA, USA.
² Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
³ UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵ University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Division of Health Analytics, Beckman Research Institute, City of Hope, Duarte, CA, USA. Electronic address: sowang@coh.org.

PMID: 39299102
DOI: 10.1016/j.cyto.2024.156753

Abstract

Introduction: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that have been linked to a number of health outcomes, including those related to immune dysfunction. However, there are limited numbers of epidemiological-based studies that directly examine the association between PFAS exposure and immune responses.

Methods: In this cross-sectional study nested in the California Teachers Study cohort, we measured nine PFAS analytes in serum. Of the 9 analytes, we further evaluated four (PFHxS [perfluorohexane sulfonate], PFNA [perfluorononanoic acid], PFOA [perfluorooctanoic acid], PFOS [perfluorooctanesulfonic acid]) that had detection levels of > 80 %, in relation to 16 systemic inflammatory/immune markers and corresponding immune pathways (Th1 [pro-inflammatory/macrophage activation], B-cell activation, and T-cell activation). Study participants (n = 722) were female, completed a questionnaire regarding various health measures and behaviors, and donated a blood sample between 2013-2016. The association between PFAS analytes and individual immune markers and pathways were evaluated by calculating odds ratios (OR) and 95 % confidence intervals (CI) in a logistic regression model. PFAS analytes were evaluated both as a dichotomous exposure (above or below the respective median) and as a continuous variable (per 1 unit increase [ng/mL]).

Results: The prevalence of detecting any PFAS analyte rose with increasing age, with the highest PFAS prevalence observed among those aged 75 + years and the lowest PFAS prevalence observed among those aged 40-49 years (study participant age range: 40-95 years). Significant associations with BAFF (B-cell activating factor) levels above the median were observed among participants with elevated (defined as above the median) levels of PFHxS (OR=1.53), PFOA (OR=1.43), and PFOS (OR=1.40). Similarly, there were statistically significant associations between elevated levels of PFHxS and TNFRII (tumor necrosis factor receptor 2) levels (OR=1.78) and IL2Rα (interleukin 2 receptor subunit alpha) levels (OR=1.48). We also observed significant inverse associations between elevated PFNA and sCD14 (soluble cluster of differentiation 14) (OR=0.73). No significant associations were observed between elevated PFNA and any immune marker. Evaluation of PFAS exposures as continuous exposures in association with dichotomized cytokines were generally consistent with the dichotomized associations.

Conclusions: PFAS exposure was associated with altered levels of circulating inflammatory/immune markers; the associations were specific to PFAS analyte and immune marker. If validated, our results may suggest potential immune mechanisms underlying associations between the different PFAS analytes and adverse health outcomes.

Keywords: B-cell activating factor (BAFF); Human population; Interleukin 2 receptor subunit alpha (IL2Rα); Perfluoroalkyl substances; Polyfluoroalkyl substances; Tumor necrosis factor receptor 2 (TNFRII).