Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real‐world investigation

• Published in: Journal of neurochemistry Vol. 159; no. 3; pp. 618 - 628
• Main Authors: Rosenstein, Igal, Rasch, Sofia, Axelsson, Markus, Novakova, Lenka, Blennow, Kaj, Zetterberg, Henrik, Lycke, Jan
• Format: Journal Article
• Language: English
• Published: New York Blackwell Publishing Ltd 01.11.2021
• Subjects: Autoimmune diseases; bands; Biochemistry & Molecular Biology; Biomarkers; Cerebrospinal fluid; cerebrospinal-fluid analysis; Chains; csf; Demographics; diagnosis; disease-activity; Immunoglobulin G; index; Inflammatory diseases; Kappa free light chain; Kappa free light chain index; kflc; mri; Multiple sclerosis; Neurosciences; Neurosciences & Neurology; Neurovetenskaper; Patients; patterns; protein; Sensitivity; utility
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/jnc.15500

Kappa free light chain (KFLC) index, a measure for intrathecal production of free kappa chains, has been increasingly recognized for its diagnostic potential in multiple sclerosis (MS) as a quantitative alternative to IgG oligoclonal bands (OCBs). Our objective was to investigate the sensitivity, specificity, and overall diagnostic accuracy of KFLC index in MS. KFLC index was prospectively determined as part of the diagnostic workup in patients with suspected MS (n = 327) between May 2013 and February 2020. Patients with clinically isolated syndrome (CIS), radiologically isolated syndrome (RIS), and MS had markedly higher KFLC index (44.6, IQR 16–128) compared with subjects with other neuro‐inflammatory disorders (ONID) and symptomatic controls (SC) (2.19, IQR 1.68–2.98, p < 0.001). KFLC index had a sensitivity of 0.93 (95% CI 0.88–0.95) and specificity of 0.87 (95% CI 0.8–0.92) to discriminate CIS/RIS/MS from ONID and SC (AUC 0.94, 95% CI 0.91–0.97, p < 0.001). KFLC index and intrathecal fraction (IF) KFLC had similar accuracies to detect MS. Treatment with disease‐modifying therapy (DMT) did not influence the level of KFLC index and it was not affected by demographic factors or associated with degenerative or inflammatory biomarkers in cerebrospinal fluid (CSF). KFLC index in MS diagnostics has methodological advantages compared to OCB and is independent to subjective interpretation. Moreover, it is an attractive diagnostic tool since the diagnostic specificity and sensitivity of KFLC index are similar with that of OCBs and KFLCIF and better than for IgG index. We show that KFLC index was influenced neither by DMT nor by demographic factors or other inflammatory or degenerative processes in MS as determined by biomarkers in CSF. We investigated the sensitivity, specificity, and overall diagnostic accuracy of Kappa Free Light Chain (KFLC)‐index in multiple sclerosis (MS). KFLC‐index was prospectively determined as part of the diagnostic workup in patients with suspected MS (n = 327) between May 2013 and February 2020. We found that KFLC‐index in MS diagnostics has methodological advantages compared to oligoclonal bands and is independent to subjective interpretation. We show that KFLC‐index was influenced neither by disease‐modifying therapy, nor by demographic factors or other inflammatory or degenerative processes in MS as determined by biomarkers in cerebrospinal fluid.