Diagnostic Utility of Kappa Free Light Chain Index in Patients with Multiple Sclerosis in India: A Cross-Sectional Study

Abstract Background and Objectives: Cerebrospinal fluid (CSF) kappa free light chains (KFLCs) are emerging biomarkers of intrathecal immunoglobulin synthesis in multiple sclerosis (MS) and have been included as supportive markers in the 2024 McDonald criteria. However, data from the Indian subcontinent remain limited. The study aimed to evaluate the diagnostic performance of the KFLC index for MS and examine its association with laboratory and magnetic resonance imaging (MRI) biomarkers. Methods: In this cross-sectional study, adults (≥18 years) with MS, inflammatory controls (neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, seronegative optic neuritis), and non-inflammatory controls (idiopathic intracranial hypertension, normal pressure hydrocephalus) were enrolled. KFLC was measured in paired CSF and serum, and the KFLC index was calculated. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis, and associations with oligoclonal bands (OCBs), IgG index, disability (EDSS), and MRI biomarkers: central vein sign (CVS) and paramagnetic rim lesions (PRL) were evaluated. Results: Forty patients were included (22 MS, 12 inflammatory controls, 6 non-inflammatory controls) over six months. KFLC index was higher in MS (median 24 [interquartile range 9–54]) than in inflammatory (4 [3–10]) and non-inflammatory controls (6 [4–7]) ( P < 0.001). ROC analysis showed good performance (area under the curve [AUC] 0.855); a cutoff of 7.40 yielded 86.4% sensitivity and 72.2% specificity. KFLC positivity demonstrated moderate concordance with OCBs (κ = 0.55). KFLC index was significantly higher in patients with CVS and PRL but showed no correlation with IgG index or EDSS. Conclusions: KFLC index shows good diagnostic performance for MS and correlates with MRI biomarkers, supporting its clinical utility in the Indian setting.