Comparing kappa free light chain index and CSF-restricted oligoclonal bands for detecting intrathecal immunoglobulin synthesis in a Norwegian cohort.

BACKGROUND: The revised McDonald criteria (2024) recommend kappa free light chain (kFLC) index as equivalent to cerebrospinal fluid (CSF)-restricted oligoclonal IgG bands (OCB) to demonstrate intrathecal immunoglobulin synthesis. A kFLC index ≥ 6.1 has been recommended to define CSF positivity. We aimed to validate kFLC index against OCB using single (6.1) and dual cutoff (3.5 and 20) strategies and propose a suitable algorithm with reflex testing. METHODS: kFLC index was evaluated with OCB as a reference standard in adults undergoing routine neurological evaluation. RESULTS: Of 1257 samples, 14% were OCB positive. A kFLC index ≥ 6.1 yielded 92% sensitivity and 94% specificity, with positive and negative predictive values of 70% and 99%. ROC-derived optimal cutoff was 5.1 with 95% sensitivity and 93% specificity. 75% had kFLC index < 3.5 with a 99.7% probability of being OCB negative. 15% had a kFLC index of 3.5-20 (28% OCB positive) and 10% had kFLC index > 20 (88% OCB positive) with discrepancies mainly due to OCB type 4 and/or one single band. The kFLC index decreased with age among OCB positive patients and was lower in men than women. CONCLUSION: The kFLC index cutoff of 6.1 aligns with OCB, but a majority with a kFLC index of 6.1-20 was OCB negative. A dual cutoff strategy (3.5 and 20) with a diagnostic grey zone may better stratify patients according to their risk of intrathecal immunoglobulin production. Omitting OCB testing for samples with a kFLC index < 3.5 will reduce OCB testing by 75%.