Kappa free light chains in multiple sclerosis - diagnostic accuracy and comparison with other markers

Aim: Kappa free light chains (kappa-fLC) in cerebrospinal fluid (CSF) were suggested as promising novel markers of intrathecal immunoglobulin (Ig) synthesis in MS patients, with reported discrepant reference values. We aimed to analyse the diagnostic accuracy of kappa-fLC (CSF concentration, quotient, index) and routinely used markers (IgG index, IgG(Reibe)(r)) in MS diagnostics, in prediction of oligoclonal bands (OCB) positivity and in OCB negative patients. Methods: Serum/CSF paired samples were analysed from 46 MS patients and 63 controls with non-inflammatory and non-MS inflammatory diseases of CNS. The concentrations of kappa-fLC were measured immunoturbidimetrically (SPA PLUS (R), Freelite (R)). The ROC curves, diagnostic sensitivities and specificities were analysed with respect to the cut-offs, which were determined using Youden's index. Results: The optimal cut-off values were defined as: 0.76 for IgG index; 0.89 mg/L for IgG(Reiber); 1.08 mg/L for CSF kappa-fLC level; 0.0994 for kappa-fLC quotient; 18.15 for kappa-fLC index. To distinguish MS patients from controls, the highest combined sensitivities/specificities were observed for kappa-fLC index (0.76/0.98), followed by kappa-fLC quotient (0.76/0.97), CSF kappa-fLC level (0.76/0.95), IgG(Reibe)(r) (0.70/0.91) and IgG index (0.65/0.89). The OCB detection showed the sensitivity 0.83 and the specificity 1.00. In prediction of OCB positivity, the novel kappa-fLC markers showed excellent diagnostic accuracy with sensitivities/specificities: 0.92/0.99 for kappa-fLC index, 0.92/0.97 for kappa-fLC quotient, and 0.92/0.96 for CSF kappa-fLC level, compared to 0.76/0.89 for IgG index and 0.76/0.86 for IgG(Reiber). Applying our cut-offs in OCB negative MS patients, the highest diagnostic sensitivity (038) was found for IgG(Re)(iber), followed by 0.13 for IgG index, and surprisingly by 0.00 for all kappa-fLC markers. Conclusion: In MS diagnostics and in prediction of OCB positivity, all novel kappa-fLC markers showed better sensitivities and specificities than routinely used IgG index and IgG mbe , but did not reach those of OCBs. To proove the intrathecal Ig synthesis in patients with suspected MS, we recommend to use kappa-fLC index and quotient along with OCB, especially if OCB findings are equivocal or negative.