Profiling peripheral blood oxidative stress in multiple sclerosis

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BACKGROUND: Oxidative stress is implicated in the pathophysiology of multiple sclerosis (MS), but the potential of oxidative stress responses as MS biomarkers has not been systematically explored. METHODS: Over 12 months, we measured serial plasma concentrations or activity, and peripheral blood mononuclear cell (PBMC) expression of master antioxidant regulators, downstream antioxidant enzymes, and plasma end products of oxidation in blood from people with MS (pwMS), including a cohort commencing disease modifying therapy (DMT). Multivariable regression models were employed adjusting for age, sex, disease duration, smoking, and repeated measures. RESULTS: 40 control subjects and 78 pwMS participants (53 relapsing-remitting MS (RRMS), 11 primary progressive MS (PPMS) & 14 secondary progressive MS (SPMS)) were included; 12 commenced dimethyl fumarate (DMF), 12 ocrelizumab and 7 natalizumab. NFE2L2 (nuclear factor erythroid 2-related factor 2; Nrf2), CAT (catalase) and GPX1 (glutathione peroxidase 1) expression were downregulated in SPMS, with increased concentration of end products of oxidation. Plasma peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) concentration was higher in pwMS. Nrf2 concentration, catalase activity and PBMC SOD1 expression increased with DMF. PBMC NFE2L2, GPX1 and SOD1 expression increased with natalizumab. Effect sizes were relatively modest and inter-individual heterogeneity was high limiting potential clinical application. No significant associations with the Expanded Disability Status Scale were observed. CONCLUSIONS: Our data support dysregulated oxidative stress responses in MS but individual oxidative stress components are unlikely to inform disease stratification and monitoring. However, a constellation of biomarkers, may have clinical utility and inform regarding MS pathophysiology and therapy.

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