Co-exposure to PFAS and hydroxylated PCBs is associated with increased odds of multiple sclerosis

Persistent organic pollutants often co-occur in human exposure environments, yet their combined effects on disease risk remain poorly understood. This study examined associations between serum concentrations of 14 per- and polyfluorinated substances (PFAS) and three hydroxylated polychlorinated biphenyls (OH-PCBs) and the onset of multiple sclerosis (MS), utilizing data from the Swedish population-based Epidemiological Investigation of Multiple Sclerosis (EIMS) cohort, comprising 907 MS cases and 907 matched controls. We employed single-substance logistic regression and quantile g-computation to evaluate cumulative and individual compound associations. We considered linear and non-linear risk patterns while adjusting for lifestyle factors and MS-associated HLA alleles. Our analysis revealed non-linear associations for several individual compounds, particularly perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid, 2,2',3,4',5,5',6-heptachloro-4-biphenylol (4-OH-CB187), and 2,2',4,4',5,5'-, Hexachloro-3-biphenylol (3-OH-CB153), with increased odds of MS. Interaction analyses further indicated that the association between PFOS and MS odds was modified by the presence of the HLA-B*44:02 allele, known for its protective effect on MS risk. Mixture modeling highlighted that combined exposures to PFAS and OH-PCBs significantly increased MS odds, even when associations for individual compounds were weak or absent. These findings emphasize the complexity of associations between environmental contaminants, lifestyle and genetic risk factors, and the odds of MS. They underscore the importance of addressing co-exposure in environmental health research and call for further studies to elucidate underlying biological mechanisms.