Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis

• Published in: Multiple sclerosis Vol. 29; no. 2; pp. 169 - 181
• Main Authors: Hegen, Harald, Walde, Janette, Berek, Klaus, Arrambide, Georgina, Gnanapavan, Sharmilee, Kaplan, Batia, Khalil, Michael, Saadeh, Ruba, Teunissen, Charlotte, Tumani, Hayrettin, Villar, Luisa M, Willrich, Maria Alice V, Zetterberg, Henrik, Deisenhammer, Florian
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.02.2023
• Subjects: Biomarkers - cerebrospinal fluid; Demyelinating Diseases; Humans; Immunoglobulin G - cerebrospinal fluid; Immunoglobulin kappa-Chains - cerebrospinal fluid; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - diagnosis; Oligoclonal Bands - cerebrospinal fluid; intrathecal fraction; multiple sclerosis; meta-analysis; diagnosis; index; Cerebrospinal fluid; kappa free light chains; biomarker; systematic review; clinically isolated syndrome
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/13524585221134213

Background: Intrathecal immunoglobulin-G synthesis is a hallmark of multiple sclerosis (MS), which can be detected by oligoclonal IgG bands (OCB) or by κ-free light chains (κ-FLC) in cerebrospinal fluid. Objective: To perform a systematic review and meta-analysis to evaluate whether κ-FLC index has similar diagnostic value to identify patients with clinically isolated syndrome (CIS) or MS compared to OCB, and to determine κ-FLC index cut-off. Methods: PubMed was searched for studies that assessed diagnostic sensitivity and specificity of κ-FLC index and OCB to discriminate CIS/MS patients from control subjects. Two reviewers following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines performed study eligibility assessment and data extraction. Findings from studies were analyzed with bivariate mixed models. Results: A total of 32 studies were included in the meta-analysis to evaluate diagnostic value of κ-FLC index. Sensitivity and specificity ranged from 52% to 100% (weighted average: 88%) and 69% to 100% (89%) for κ-FLC index and from 37% to 100% (85%) and 74% to 100% (92%) for OCB. Mean difference of sensitivity and specificity between κ-FLC index and OCB was 2 and −4 percentage points. Diagnostic accuracy determined by mixed models revealed no significant difference between κ-FLC index and OCB. A discriminatory cut-off for κ-FLC index was determined at 6.1. Conclusion: The findings indicate that κ-FLC index has similar diagnostic accuracy in MS as OCB.