Title: K index utility as diagnostic and prognostic biomarker in the assessment of patients with suspected Multiple Sclerosis

Abstract

I dentification of early biomarkers in Multiple Sclerosis (MS) is crucial for providing more individualized treatments. Cerebrospinal fluid (CSF) immunoglobulin (Ig) free light chains (FLC) are a quantitative, reliable, rater-independent measure of intrathecal immune reaction. In literature, CSF FLC showed a certain MS specificity and, more interesting, some predictive power for MS course, but the wide variability between methods and results and the use of different FLC indices complicate comparison between studies and the detection of quantitative prognostic cut-offs. The aim of our research is to evaluate the role of FLC in the initial assessment of Multiple Sclerosis (MS) patients and to select the best index and cut-offs exportable in clinical practice. We analysed CSF/serum samples of 140 patients and followed-up the CIS/MS subgroup for 7 years. Our results suggest κ index as a quantitative diagnostic and prognostic biomarker in MS, significantly associated to baseline lesion load and to successive clinical course. We propose k index ≥ 106 as a prognostic cut-off to select patients at major risk of relapse, potentially influencing initial therapeutic decisions. Our initial evidence opens the discussion on hotly debated topics, such us the need/not need of CSF sample in suspected MS, the relative role of intrathecal B-cell immune response and of blood-brain barrier damage in MS, the reason of “kappa” versus “lambda” FLC prevalence in MS patients, the usefulness of quantitative biomarkers and specific cut-offs in MS clinical management.