Kappa Free Light Chain Index in the Real World-Do We Miss Clinically Relevant Information by Skipping Oligoclonal...

No standardized strategy for integrating κ-free light chain (κ-FLC) index into routine cerebrospinal fluid (CSF) diagnostics has yet been established.

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.

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.

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.

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.