Optimizing kappa free light chain index thresholds for multiple sclerosis (MS) diagnosis in low-MS prevalence regions: Insights from an Asian cohort

Abstract

Background: The kappa free light chain (KFLC) index is a quantitative marker of intrathecal immunoglobulin synthesis with diagnostic performance comparable to cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCBs). Its utility in Asian populations, where multiple sclerosis (MS) is less prevalent and mimics such as neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease (MOGAD) are common, remains underexplored.Objectives: We aimed to validate the KFLC index and determine optimal thresholds for MS diagnosis in a Korean cohort.Methods: We retrospectively analyzed 208 patients undergoing CSF evaluation, including 103 with MS and 105 with non-MS conditions (64 NMOSD, 14 MOGAD, 27 others). KFLC-related biomarkers were compared, and receiver operating characteristic analyses identified thresholds.Results: When comparing the MS group (n = 103) with the non-MS group (n = 105), the optimal KFLC index threshold was >= 12.6, yielding sensitivity 84%, specificity 74%, and accuracy 79%. Combining KFLC index >= 12.6 with OCB positivity increased specificity to 93%. Sex-specific thresholds (>= 22.8 for females, >= 7.0 for males) improved performance, increasing male sensitivity and female specificity reaching 82%.Conclusion: The KFLC index is a reliable biomarker for MS diagnosis in Asian populations. Optimized and sex-specific thresholds may enhance diagnostic precision where MS mimics are relatively prevalent, consistent with diagnostic performance globally.