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Profiling peripheral blood oxidative stress in multiple sclerosis.

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Summary
This summary is machine-generated.

Oxidative stress responses are altered in multiple sclerosis (MS). While individual biomarkers are not useful for MS stratification, a combination may offer clinical utility and insights into MS pathophysiology and treatment.

Keywords:
AntioxidantBiomarkersMultiple sclerosisNrf2Oxidative stressPGC-1α

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Area of Science:

  • Neuroimmunology
  • Biomarker Discovery
  • Oxidative Stress Research

Background:

  • Oxidative stress is implicated in multiple sclerosis (MS) pathophysiology.
  • The utility of oxidative stress responses as MS biomarkers remains underexplored.

Purpose of the Study:

  • To systematically investigate oxidative stress responses as potential biomarkers in people with MS (pwMS).
  • To assess changes in antioxidant regulators and oxidation products in relation to MS subtypes and disease-modifying therapies (DMTs).

Main Methods:

  • Serial measurements of plasma and peripheral blood mononuclear cell (PBMC) markers of oxidative stress in pwMS and controls over 12 months.
  • Analysis included antioxidant regulators, enzymes, and oxidation end products, with multivariable regression adjusting for clinical factors.
  • Included cohorts commencing dimethyl fumarate (DMF), ocrelizumab, or natalizumab.

Main Results:

  • Downregulation of NFE2L2 (nuclear factor erythroid 2-related factor 2), CAT (catalase), and GPX1 (glutathione peroxidase 1) expression observed in secondary progressive MS (SPMS).
  • Increased plasma peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in pwMS; Nrf2, catalase activity, and SOD1 expression increased with DMF.
  • PBMC NFE2L2, GPX1, and SOD1 expression increased with natalizumab, but effect sizes were modest with high heterogeneity.

Conclusions:

  • Data support dysregulated oxidative stress in MS, but individual markers are unlikely to stratify or monitor disease.
  • A constellation of oxidative stress biomarkers may hold clinical utility for understanding MS pathophysiology and guiding therapy.