A sex-dependent algorithm including kappa free light chain for multiple sclerosis diagnosis

Abstract

Multiple sclerosis (MS) diagnosis includes the presence of restricted oligoclonal bands (OCB) in cerebrospinal fluid (CSF), but it has several limitations, as it is an observer-dependent time-consuming technique and offers a dichotomous result. Thus kappa free light chains (KFLC) have emerged as a quantitative alternative. However, the cut-off values for KFLC have not been well established yet and it is not clear if differences between sexes exist. We aim to evaluate these and to compare the diagnostic accuracy of KFLC concentrations and their related indexes versus OCB. For that purpose, paired CSF and serum samples were collected and immediately processed for albumin, total protein, immunoglobulins and OCB, then frozen at -20 degrees C. KFLC was measured in a BN II (Siemens Healthineers, Germany). KFLC-derived indexes were calculated. Diagnostic accuracy was evaluated by the area under the curve (AUC), Youden's index and odds ratio. From the 193 patients included, 56 were classified as MS according to the 2017 McDonald criteria. K-index, Q KFLC and Reiber's diagram showed good accuracy in MS diagnosis when studied distinguishing between sexes, similar to OCB. Cut-offs for K-index and Q KFLC change substantially between sex having the highest AUC similar than OCB. A sex-dependent algorithm combining the use of K-index, Q KFLC and OCB yields the highest diagnostic accuracy. In conclusion, CSF KFLC measurement is a rapid, quantitative and easy-to-standardize tool that used through the proposed sex-dependent algorithm may reduce the number of manual OCB tests performed.