Per-/polyfluoroalkyl substance concentrations in human serum and their associations with immune markers of rheumatoid arthritis

Per-/polyfluoroalkyl substances (PFASs) are ubiquitous in the environment and have been proved to be immunotoxic to humans. However, it remains unclear whether exposure to PFASs affects the risk of rheumatoid arthritis (RA). In this study, nine PFASs were determined in human serum collected from 280 health populations and 294 RA patients in a cohort enrolled between 2018 and 2020 in Hangzhou, China, and were examined their correlations with immune marker levels. Perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were the predominant PFASs in human serum, with median (mean) concentrations of 5.4 (7.6), 2.8 (3.5), and 1.9 (2.5) ng/mL, respectively. Serum PFOA and 6:2 Cl-PFESA concentrations were positively correlated with anti-cyclic citrullinated peptide antibody (ACPA) (βPFOA = 0.59, 95% confidence interval (CI): 0.37, 0.81; β6:2 Cl-PFESA = 0.48, 95% CI: 0.29, 0.66), immunoglobulin G (βPFOA = 0.25, 95% CI: 0.21, 0.29; β6:2 Cl-PFESA = 0.16, 95% CI: 0.12, 0.19) as well as rheumatoid factors (RF) (βPFOA = 0.57, 95% CI: 0.34, 0.80; β6:2 Cl-PFESA = 0.54, 95% CI: 0.36, 0.72). The correlations between serum PFOS levels and RF (β = 0.52, 95% CI: 0.28, 0.77), ACPA (β = 0.48, 95% CI: 0.23, 0.73), as well as immunoglobulin M (β = -0.24, 95% CI: 0.64, 0.15) respectively were statistically stronger. We also found PFOA concentrations in serum were associated with the level of C-reactive protein (β = 0.52, 95% CI: 0.40, 0.65). To our knowledge, this is the first study reporting significant associations between several PFASs and change of specific immune marker levels, suggesting that PFAS exposure may increase the risk of RA in adults.