Kappa free light chain concentration in serum is reduced after CD20-depletion with ocrelizumab.

Background: Kappa free light chains (KFLC), a byproduct of immunoglobulin (Ig) synthesis by B-lineage cells, can serve as an indicator for inflammatory activity. In multiple sclerosis (MS), especially the intrathecal KFLC production has gained increasing importance as a biomarker for central nervous system (CNS) inflammation and was included into the proposed 2024 revision of the McDonald criteria. In contrast, studies investigating the significance of KFLC in serum and the effects of disease-modifying therapies (DMT) on KFLC serum concentration in MS are rare. The aim of the present work was to investigate the impact of B cell depletion with ocrelizumab on KFLC concentrations in serum of MS patients and the ability of serum KFLC to monitor disease activity.

Methods: 50 MS patients were included in the present study- 38 with the diagnosis of relapsing MS (RMS) and 12 with diagnosis of primary-progressive MS (PPMS) -, who were treated with ocrelizumab for two years. Serum concentrations of albumin, immunoglobulins and KFLC as well as lymphocyte subsets were determined at baseline and after two years.

Results: Serum Ig and KFLC concentrations were found to be significantly lower after two years of ocrelizumab treatment (mean serum concentrations: KFLC: 9.5 mg/l vs. 7.8 mg/l, p = 0.0003; IgG: 9 g/l vs. 8 g/l, p = 0.0002; IgA: 2 g/l vs. 1.8 g/l, p = 0.0010; IgM: 1.8 g/l vs. 0.7 g/l, p < 0.0001). Serum KFLC concentration did not correlate with clinical and paraclinical parameters of disease activity.

Conclusions: Treatment with ocrelizumab reduces serum KFLC concentration in MS patients. However, serum KFLC concentration is not able to predict disease activity in these MS patients.