Kappa index for multiple sclerosis diagnosis: an accurate biomarker of intrathecal synthesis

Background: Cerebrospinal fluid (CSF) kappa-free light chains (KFLC) are becoming a diagnostic biomarker for multiple sclerosis (MS). Objectives: We aimed to compare the diagnostic performance of intrathecal synthesis biomarkers to that of oligoclonal bands (OB) in diagnosing MS, radiological and clinical isolated syndromes (RIS-CIS) on a large cohort of patients collected over 10 years. Methods: We collected 1124 patients (58% females) in 10 years who underwent CSF analysis for intrathecal synthesis in the diagnostic work-up, and they were classified according to their diagnosis as 417 MS, 287 with other neurological inflammatory disorders (including 76 RIS-CIS), and 420 non-inflammatory diseases (excluding lymphoproliferative and infective diagnosis). Results: MS patients significantly differ from all other groups (including if considering the RIS-CIS cohort) for CSF KFLC, KFLC intrathecal fraction (IF), Kappa index, and OB. Evaluating the diagnostic performance, the Kappa index cut-off was 6.4 for diagnosing MS and 5.7 for predicting OB. A diagnostic algorithm could avoid IEF if the Kappa index is higher than 20. Conclusions: The KFLC index confirmed its accuracy for MS diagnosis in this large Italian cohort, adding information also in the RIS-CIS population.