Kappa free light chains as a biomarker in multiple sclerosis

Introduction. Mulple Sclerosis (MS) cerebrospinal fluid (CSF) hallmarks are increased intrathecal immunoglobulins (Ig) and free light chains of kappa subtype (KFLC). Aims . To evaluate KFLC towards MS diagnosis and prognosis. Methods. We enrolled subjects who underwent CSF study in their diagnosc work up at the Novara University Hospital. KFLC were measured in CSF and serum by nephelometry to calculate kappa index:(CSF KFLC/serum KFLC)/(CSF albumin/serum albumin). Results. First, CSF KFLC were significantly higher in MS versus not-MS, and we defined a cut-off of 5 for kappa index in a ROC analysis. Moreover, oligoclonal bands (OB: gold-standard method to detect intrathecal synthesis) and kappa index had similar accuracy in diagnosing MS. We introduced in clinical pracce the sequenal use of kappa index (first test) and OB (confirmave procedure) as quick, accurate, less expensive and not-related operators’ interpretaon. Secondly, we compared the efficiency of KFLC to IgG (or Link) index (as the rao of CSF/serum IgG and albumin, historically used as quantave marker of MS intrathecal synthesis), and using KFLC through different interpretaon approaches. Despite OB were confirmed to be a gold-standard, the KFLC, calculated as kappa index, confirmed their accuracy in MS diagnosis. Thirdly, concerning the prognosc value of intrathecal synthesis, we evaluated the role of KFLC in predicng MS early progression. Kappa index resulted in a significant predictor for disability being higher in paents who developed greater MS severity score (a measure of disability over me) at last follow up. We then evaluate the prognosc value of KFLC in radiologically and clinically isolated syndromes (RIS-CIS). RIS-CIS paents who converted to MS showed greater kappa index and CSF KFLC/IgG, being this laer (not including serum) more significant. Conclusions : A “kappa- oriented” response characterizes MS and has a prognosc impact in the early disease course.