ArticleFrontiers in immunology2026
A glial oxidative signature predicts disability in primary progressive multiple sclerosis and is associated with long-term cognitive decline.
Article in Frontiers in immunology, 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: Progressive multiple sclerosis (MS) involves heterogeneous mechanisms, and primary progressive MS without inflammatory activity (PPMS-NA) is poorly understood. Objective: To characterize the immune-oxidative profile of PPMS-NA and assess plasma IL-6, IL-8, IFNα2, and cerebrospinal fluid (CSF) reactive oxygen species (ROS) as predictors of disability and cognitive decline. Methods: We conducted a multicenter longitudinal study with two cohorts. Cohort 1 included participants across MS phenotypes (n = 146 baseline; n = 36 follow-up) and other neurological disorders, measuring plasma cytokines and CSF ROS. Cohort 2 included 40 people with MS, followed for 10 years to assess associations with cognition. Outcomes were analyzed with multivariate models. Results: PPMS-NA showed reduced IL-6 and IFNα2 but elevated CSF ROS versus RRMS and OND, reflecting low systemic inflammation and central oxidative stress. IL-8 increased, predicting disability and 10-year processing speed decline. IL-6 had time- and domain-specific effects: initially linked to attention, later inversely with visuospatial and working memory. CSF ROS correlated with atrophy, supporting oxidative stress as neurodegeneration driver. Conclusion: PPMS-NA is a progressive MS subtype driven by oxidative and glial processes. IL-8 and CSF ROS are biomarkers for early stratification, and IL-6 relates to cognition, supporting therapies targeting oxidative stress and glia.
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