Kappa free light chain index in multiple sclerosis and other inflammatory CNS diseases: a pilot single-center study from Argentina

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.