Kappa free light chain index as a diagnostic and prognostic biomarker in multiple sclerosis

Abstract

Background The proposed 2024 McDonald criteria incorporate the kappa free light chain (KFLC) index as an additional biomarker in multiple sclerosis (MS) diagnosis. Emerging evidence suggests that a high KFLC index may relate to worse outcomes in people with MS (pwMS). This study had two main objectives: to evaluate the diagnostic performance of the KFLC index against the 2017 and proposed 2024 clinico-radiological McDonald criteria, and to explore its prognostic significance. Methods We performed a retrospective cohort study of adults with a first episode suggestive of MS (2019–2024). All underwent lumbar puncture with simultaneous determination of the KFLC index and oligoclonal bands (OCB). Results Among 150 participants, OCB showed sensitivities of 85.9% (2017) and 86.6% (2024) with specificities of 79.7% and 81.9%. A KFLC index cut-off of 12.0 yielded sensitivities of 87.5% (2017) and 88.1% (2024) with specificities of 79.2% and 81.4%, comparable to OCB. In pwMS, KFLC index ≥ 100 was associated with younger age (OR 1.53, p = 0.048), women (OR 1.53, p = 0.037), relapses (OR 2.30, p = 0.029) and new infratentorial or spinal cord (SC) lesions (OR 6.90, p = 0.003). In multivariable analysis, KFLC index ≥ 100 remained associated with new infratentorial or SC lesions (aOR 8.07, p = 0.019). Conclusion The KFLC index shows diagnostic utility comparable to OCB; however, it is an adjunctive biomarker that complements clinical and MRI findings and should not be used as a standalone diagnostic test. An elevated KFLC index was associated with short-term accrual of infratentorial or SC lesions; these exploratory findings require validation in larger, longer-term cohorts.