CSF Kappa Free Light Chain: An enhancement to Oligoclonal Bands? A Tertiary Centre Cohort

Background Measurement of kappa free light chains (κFLC) in cerebrospinal fluid (CSF) has been demonstrated as a quantitative biomarker for neuroinflammation. CSF κFLC may be displayed in several forms, often using a peripheral κFLC measurement as a denominator to highlight intrathecal rather than systemic inflammation. This study seeks to contextualise CSF κFLC as an alternative to oligoclonal band (OCB) analysis. Methods Patient samples were separated into 2 distinct cohorts by clinical diagnosis and OCB result. κFLC, IgG, albumin and OCB were analysed for paired CSF and serum samples (n=104); CSF cell counts were also performed. Quotient calculations for κFLC were performed and hyperbolic reference curves drawn. Results Comparison of κFLC and OCB results showed that samples with 2 or more unmatched OCB gave significantly different CSF κFLC determinations in all κFLC result formats (p <0.001) compared with other OCB cohorts. CSF κFLC also correlated with ≥1 unmatched OCB. All multiple sclerosis (MS) patients gave significantly different κFLC determinations in all κFLC result formats (p <0.001) between MS and non-MS cohorts. Using a κFLC index cut-off ≥16 gave PPV and NPV of 85% and 94% for MS. Conclusions CSF κFLC has been incorporated into the 2024 revision of the McDonald Criteria. This study supports CSF κFLC as a quantitative, non-specific biomarker for MS. Advantages of κFLC in a laboratory repertoire include simple analysis available on common analytical platforms. We recommend that CSF κFLC should be used in conjunction with OCB for samples without a clear positive or negative result.