Tuesday, 13 October 2026

Veiga JL, Monreal E, Espiño M, Chico JL, Fernández JI, Rodríguez F, Villarrubia N, Rodero A, Sainz de la Maza S, Masjuan J, Costa L, Villar LM. Kappa index: real-world study for assessing cut-off values that provide the best accuracy for multiple sclerosis diagnosis in patients with CIS

Front Immunol. 2026

“Combining the kappa index and OCB with CIS topography clearly improve diagnostic accuracy in CIS, allowing an early and reliable MS diagnosis". - José Luis Veiga-González & Dr Luisa María Villar

Summary:

Background: Intrathecal immunoglobulin G synthesis (ITGS) is important for MS diagnosis. Oligoclonal bands (OCB) have demonstrated sensitivity and specificity, but their complexity necessitates their analysis in specialized laboratories. Measuring the kappa free light chain index emerged as an automated and reproducible alternative and was incorporated as an alternative to OCB in the 2024 McDonald criteria. However, establishing the optimal cut-off for predicting MS diagnosis in patients with clinically isolated syndrome (CIS) is needed.

Methods: We included 391 patients with CIS recruited between 2017 and 2022 who were followed for at least three years. Cerebrospinal fluid and serum samples were analyzed for OCB and the kappa index. Sensitivity, specificity, positive and negative predictive values were calculated for multiple kappa index cut-offs (6.1-20) and compared with OCB, the IgG index, and Reiber formulae. Subgroup analyses were performed according to CIS topography.

Results: A cut-off value of 15, with OCB assessment in cases with lower values, gave the best results in the total cohort, with sensitivity and specificity higher than 90%. However, subgroup analysis revealed two patterns depending on CIS location. In all locations except the optic nerve, Reiber formulae gave excellent results, comparable to those of OCB. Conversely, in patients with optic neuritis, Reiber formulae and the kappa index gave low specificity. The best strategy for these patients was a kappa index cut-off value of 15, with OCB assessment for lower values, or OCB alone.

Conclusion: The optimal semiquantitative method for detecting kappa intrathecal synthesis for predicting MS in patients with CIS depends on CIS topography. A positive value for Reiber formulae or a cut-off of 6.1 provides diagnostic performance comparable to OCB in non-optic neuritis CIS, reducing the need for OCB analysis. In optic neuritis, OCB assessment alone or in conjunction with a kappa index cut-off of 15 offered the best diagnostic accuracy.

Why do you highligth this publication?

This real-world study evaluated the diagnostic performance of different kappa index cut-offs in 391 patients with CIS. Increasing the kappa index cut-off to 15 led to an increase in specificity, while combining KI ≥15 with OCB increased sensitivity to 96.6% without reducing specificity. Importantly, diagnostic performance varied according to CIS topography, particularly in patients presenting with optic neuritis, highlighting the potential value of a topography-adapted approach to KFLC interpretation.