Background: It was found in previous studies that abnormal cerebrospinal fluid (CSF) κFLC (kappa free light chain) and κ index levels were associated with increased probability of CIS conversion to Multiple sclerosis (MS) and also accurate diagnosis. However, still, the value of κFLC and κ index for MS diagnosis remains controversial. In this systematic review and metaanalysis study, we aimed to evaluate the diagnostic value of CSF κFLC and κ index for MS. Methods: Three electronic databases including PubMed, Scopus, and Web of Science were searched for published literature and reviewed abstracts. We included studies that measured and reported CSF κFLC level or κ index in adults with MS. Results: After a two-step review, 31 studies with a total of 9324 subjects were included in our qualitative and quantitative synthesis. Our analysis showed that the overall sensitivity and specificity of CSF κFLC in the diagnosis of MS from other groups was 85% (CI: [0.77-0.90]) and 90% (CI: [0.82-0.95]). Further analysis for the κ index demonstrated sensitivity and specificity of 90% (CI: [0.88-0.92]) and 87% (CI: [0.84-0.90]) for detecting MS from all other groups. Metaanalysis showed that the sensitivity and specificity of the κ index in the diagnosis of MS from other groups was 91% (CI: [0.89-0.92]) and 86% (CI: [0.83-0.88]) while the area under the curve (AUC) was 0.94 when the cut-off point was lower than 8. Also, at the cut-off point>8, the sensitivity and specificity were 87% (CI: [0.80-0.91]) and 90% (CI: [0.81-0.95]) and AUC was 0.93. Conclusion: Our meta-analysis revealed that both the κFLC and κ index are effective biomarkers for distinguishing MS from other neurological diseases. Our results also showed that the κ index is significantly higher in MS patients compared to patients with other inflammatory and noninflammatory neurological diseases. Thus, we strongly recommend incorporating the κ index into MS diagnosis protocols.
