Kappa Free Light Chain Index in the Real World—Do We Miss Clinically Relevant Information by Skipping Oligoclonal Banding?

ABSTRACT 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.