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

Cerebrospinal fluid (CSF) kappa-free light chains (KFLC) are becoming a diagnostic biomarker for multiple sclerosis (MS).

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.

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).

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.

The KFLC index confirmed its accuracy for MS diagnosis in this large Italian cohort, adding information also in the RIS-CIS population.