Fluid biomarkers in multiple sclerosis: Indicators of disease activity, progression, and treatment response

Multiple sclerosis (MS) is a chronic immune-mediated CNS disorder marked by inflammation, demyelination, and neurodegeneration. Standard clinical evaluation, neurological exams, disability scoring, and MRI often miss subclinical activity and poorly predict progression. Fluid biomarkers in cerebrospinal fluid (CSF) and blood provide objective, quantifiable indicators of disease activity, progression, and therapeutic response. Essential fluid biomarkers for monitoring MS include neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Chitinase-3-like protein 1 (CHI3L1), C-X-C Motif Chemokine 13 (CXCL13), osteopontin (OPN), leptin, brain-derived neurotrophic factor (BDNF), and copeptin. NfL reflects axonal injury and correlates with lesion burden, relapse frequency, and long-term disability. At the same time, GFAP and CHI3L1 track astroglial activation and neurodegeneration, which aid the differentiation between relapsing-progressive forms. CXCL13 and OPN also capture intrathecal immune activity. Ultrasensitive assays allow reliable detection of low-abundance CNS proteins in blood, enabling longitudinal monitoring. Altogether, integrating biomarker panels improves prognostication, guides treatment selection, and assesses the efficacy of disease-modifying therapy. Future studies should prioritize establishing robust reference ranges and accounting for demographic and physiological confounders to ensure accurate clinical application.