Kappa Free Light Chain Index Correlates With Prognostic Biomarkers in Multiple Sclerosis and Decreases Slowly Following Treatment

OBJECTIVE: To investigate the relation between intrathecal antibody production, as reflected by kappa free light chain (KFLC) metrics, and multiple sclerosis (MS) prognosis-related markers and study its modulation following MS treatment. METHODS: This study comprised matched plasma and cerebrospinal fluid (CSF) samples from a total of 130 persons with MS (pwMS), 99 of whom were untreated at baseline. Paired samples from 73 pwMS (18 on dimethyl fumarate (DMF), 10 on fingolimod, 6 on natalizumab, 25 on rituximab (RTX) and 14 after autologous hematopoietic stem cell transplantation (HSCT)) were used to analyze treatment effects on KFLC metrics. KFLC was measured by nephelometry while clinical and paraclinical data were collected from the patient charts. HLA typing was performed with SNP genotyping. RESULTS: The KFLC local concentration (KFLC loc) and index was higher in HLA-DRB1*15:01 carriers and correlated with the number of CSF mononuclear cells, IgG index, and CSF levels of CXCL13 and neurofilament light chain, the latter particularly during remission (r = 0.27, p = 0.045). With regard to treatment effects, we found that treatment with DMF, RTX, and HSCT resulted in a decrease of CSF-KFLC levels and/or KFLC loc and index. Interestingly, the rate of decrease in KFLC index correlated with time since first treatment (r = -0.41, p = 0.045). CONCLUSION: These findings support an involvement of intrathecal antibodies in non-relapsing MS pathology and inform on the effect of current treatments. The slow rate of decrease in KFLC index following B cell depletion stresses the need for early treatment start.