Decreased Intrathecal Concentrations of Free Light Chains Kappa in Multiple Sclerosis Patients Taking Very High Effective Disease-Modifying Treatment

Free light chains kappa (FLC kappa) in cerebrospinal fluid (CSF) are a part of the intrathecal immune response. This observational study was conducted to investigate the effects of different disease-modifying therapies (DMT) on the humoral intrathecal immune response in the CSF of patients with multiple sclerosis (MS). FLC kappa were analyzed in CSF and serum samples from MS patients taking DMT (n = 60) and those in a control cohort of treatment-naive MS patients (n = 90). DMT was classified as moderately effective (including INF beta-1a, INF beta-1b, glatiramer acetate, dimethyl fumarate, teriflunomide, triamcinolone); highly effective (including fingolimod, daclizumab) and very highly effective (alemtuzumab, natalizumab, rituximab/ocrelizumab, mitoxantrone). FLC kappa were measured using a nephelometric FLC kappa kit. Intrathecal FLC kappa and IgG concentrations were assessed in relation to the hyperbolic reference range in quotient diagrams. Intrathecal FLC kappa concentrations and IgG concentrations were significantly lower in samples from the cohort of MS patients taking very highly effective DMT than in samples from the cohort of MS patients taking highly effective DMT and in the treatment-naive cohort (FLC kappa: p = 0.004, p < 0.0001 respectively/IgG: p = 0.013; p = 0.021). The reduction in FLC kappa could contribute to an anti-inflammatory effect in the CNS through this mechanism. There was no difference in the appearance of CSF-specific oligoclonal bands (p = 0.830). Longitudinal analyses are required to confirm these results.

Automated summary

This observational study investigated the effects of different disease-modifying therapies (DMT) on the humoral intrathecal immune response in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. The results showed that highly effective DMT significantly reduced the concentrations of FLC kappa and IgG in the CSF, which may contribute to an anti-inflammatory effect in the central nervous system (CNS). There was no difference in the appearance of CSF-specific oligoclonal bands.