ArticleFrontiers in immunology2026
Kappa free light chain index in multiple sclerosis and other inflammatory CNS diseases: a pilot single-center study from Argentina.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Intrathecal immunoglobulin synthesis is a hallmark of multiple sclerosis (MS) and can be assessed using the kappa free light chain (κ-FLC) index. Although widely adopted, the optimal diagnostic cut-off of the κ-FLC index may vary according to the clinical context and comparison group. Objective: To evaluate the diagnostic performance of the κ-FLC index for MS in a real-world series including inflammatory and non-inflammatory neurological disorders. Methods: We conducted a retrospective cross-sectional study including consecutive patients aged ≥16 years undergoing diagnostic lumbar puncture at a tertiary public hospital in Argentina. Patients were classified as MS/clinically isolated syndrome (MS/CIS), other inflammatory neurological diseases (OIND), or non-inflammatory neurological diseases (NIND). κ-FLC, IgG, and albumin were measured in paired cerebrospinal fluid and serum samples, and κ-FLC index was calculated using quotient-based normalization. In addition, intrathecal κ-FLC synthesis was assessed using the hyperbolic Reiber diagram (Reiber's diagram). Diagnostic performance was assessed using receiver operating characteristic (ROC) curves, with cut-off values derived from Youden's index and compared with previously proposed thresholds. Results: A total of 124 patients were included (49 MS/CIS, 48 OIND, 27 NIND). Median κ-FLC index values were significantly higher in MS/CIS compared with OIND and NIND (p < 0.001). In the primary comparison between MS/CIS and OIND, the optimal κ-FLC index cut-off was 14.6, yielding a sensitivity of 73.5% and a specificity of 68.1%. The lower threshold of 6.1 showed higher sensitivity (85.7%) but limited specificity (35.4%), while Reiber's diagram for κ-FLC showed the highest sensitivity (91.8%) but lower specificity (45.8%). Conclusions: The κ-FLC index is a valuable quantitative biomarker of intrathecal immunoglobulin synthesis in MS. In our setting, a higher κ-FLC index threshold provided a more balanced diagnostic profile, whereas Reiber's diagram favored sensitivity. Higher κ-FLC index thresholds may improve diagnostic specificity in real-world clinical settings and should be validated in independent series.
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