Background: No standardized strategy for integrating κ‐free light chain (κ‐FLC) index into routine cerebrospinal fluid (CSF) diagnostics has yet been established.Objective: To determine agreement between κ‐FLC index and CSF‐restricted oligoclonal bands (OCB), and to identify κ‐FLC index range where second‐line OCB testing is needed.Methods: A retrospective analysis was conducted in patients who had κ‐FLC measurement between December 2023 and December 2024 at the Medical University of Innsbruck. κ‐FLC in CSF and serum was determined by nephelometry; OCB by isoelectric focusing and immunoblotting. The threshold for positivity was defined as ≥ 3 CSF‐restricted bands for OCB and ≥ 6.1 for κ‐FLC index.Results: In 632 included samples, κ‐FLC index ranged from 0.5 to 971. Among 213 samples with κ‐FLC index ≥ 3.5, 180 (85%) samples had a positive κ‐FLC index and 148 (69%) positive OCB. Thirty‐four (16%) samples showed discordant results. One sample was OCB positive/κ‐FLC index negative, showing markedly elevated serum κ‐FLC values. Thirty‐three samples were OCB negative/κ‐FLC index positive; of those, 4 samples had isolated intrathecal immunoglobulin M or A synthesis, and the remaining 29 discordant samples showed a median κ‐FLC index of 8.7 (75th percentile: 10.3). The predictive value for OCB positivity exceeded 95% in the case of κ‐FLC index > 20.Conclusion: κ‐FLC index shows high agreement with OCB. Discordant results were largely confined to κ‐FLC index between 3.5 and 20 (“gray zone”). A reflex approach, that is, initial screening with κ‐FLC index and in case of values within the “gray zone” performing OCB, seems reasonable.

Anti-CD20 therapies decrease the humoral response to SARS-CoV-2 immunization. We aimed to determine the extent of the humoral response to SARS-CoV-2 antigens in correlation with peripheral B-cell dynamics among patients with central nervous system inflammatory disorders treated with anti-CD20 medications. We retrospectively included patients receiving anti-CD20 therapy after antigen contact who were divided into responders (>7 binding antibody units (BAU)/mL) and non-responders (<7 BAU/mL). In participants with first antigen contact prior to therapy, we investigated the recall response elicited once under treatment. We included 80 patients (responders n = 34, non-responders n = 37, recall cohort n = 9). The B-cell counts among responders were significantly higher compared to non-responders (mean 1012 cells/µL ± SD 105 vs. mean 17 cells/µL ± SD 47; p < 0.001). Despite very low B-cell counts (mean 9 cells/µL ± SD 20), humoral response was preserved among the recall cohort (mean 1653 BAU/mL ± SD 2250.1) and did not differ significantly from responders (mean 735 BAU/mL ± SD 1529.9; p = 0.14). Our data suggest that peripheral B cells are required to generate antibodies to neo-antigens but not for a recall response during anti-CD20 therapy. Evaluation of B-cell counts and pre-existing SARS-CoV-2 antibodies might serve as biomarkers for estimating the immune competence to mount a humoral response to SARS-CoV-2 antigens.