ArticleEnvironmental research2026
Associations between perfluoroalkyl substances and multiple sclerosis in U.S. cohorts compared with NMOSD, MOGAD, and healthy controls.
Article in Environmental research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
objectivesPerfluoroalkyl substances (PFAS) are persistent environmental contaminants with endocrine and neuroimmune properties, yet relevance to multiple sclerosis (MS) remains unclear. Recent European data suggested MS-PFAS associations may vary by sex. We evaluated sex-stratified and disease-specific PFAS-MS associations in U.S. cohorts and explored endocrine and transcriptomic correlates.
methodsLiquid chromatography-mass spectrometry-derived serum PFHxS, PFOA, and PFOS were quantified in 439 participants (226 MS, 106 healthy controls [HC], 59 neuromyelitis optica spectrum disorder [NMOSD], 48 myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]) across two U.S. cohorts. PFAS levels were compared across diagnostic groups with sex stratification. Exposure-risk models estimated MS odds. Among MS-HC females, associations between PFAS and sex-steroid metabolites were evaluated, and PFAS-correlated gene-expression signatures were examined in a subset of MS females.
resultsPFHxS was consistently elevated in MS females compared with HC, NMOSD, and MOGAD females, while PFOA showed a similar but less uniform pattern; male associations were imprecise. Exposure-risk models demonstrated dose-response and non-linear associations for PFHxS, with directionally similar patterns for PFOA; PFHxS was the primary contributor in mixture analyses. PFOS associations were weaker and less consistent. Exploratory analyses observed significant MS × PFOA interactions for several steroid metabolites, and PFAS-correlated genes showed tentative enrichment of neuronal membrane pathways.
conclusionsAcross two U.S. cohorts, PFHxS demonstrated consistent association with MS, particularly among females, while PFOA showed a similar but less uniform pattern. Exploratory findings suggest plausible pathways linking PFAS exposure to MS. Multi-ethnic and longitudinal studies are needed to expand generalizability and clarify temporality and causality.
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