Diagnostic value of IgG and free light chain quantification in CSF of patients with multiple sclerosis

Background: Quantitative measurements of multiple sclerosis (MS) markers by automated nephelometry deliver rapid and reproduceable results. As the widely used IgG index generally shows low sensitivity and specificity, new quantitative markers are needed to assist MS diagnostics. Recent studies demonstrate elevated levels of free kappa and lambda light chains in the cerebrospinal fluid (CSF) of MS patients. Objective: Our purpose was to determine the diagnostic performance of free light chains and IgG and whether different index calculations incorporating these markers increase their diagnostic value in our cohort. Methods: CSF and serum samples from 438 unselected patients, including an MS group of 70 patients (41 MS, 29 CISSMS), were analysed using nephelometry (Behring ProSpec; free light chain immunoassay of Freelit, The Binding Site, Birmingham, UK). We then retrospectively correlated results with the patients' diagnoses. Results: Best diagnostic performance is achieved using the free kappa light chain index: sensitivity 0.96; specificity 0.86. The sensitivity (0.83) and the specificity (0.81) of the free lambda light chain index are distinctly lower compared to the free kappa light chain index. However, these values still outperform the results for the IgG index (sensitivity 0.8 and specificity 0.77). Combined indices incorporating two or three of these markers cannot exceed a sensitivity of 0.96 but show significantly lowered specificities. Conclusions: In this study an elevated free kappa light chain index represents the most sensitive and specific quantitative diagnostic parameter for MS. As it is measured by automated, routinely available methods the quantification of free kappa light chains can provide a rapid and reproducible indication of intrathecal immunological process supporting current MS diagnostic criteria.