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Licensed Unlicensed Requires Authentication Published by De Gruyter July 28, 2018

Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis

  • Mikael Christiansen , Mikkel Carstensen Gjelstrup , Morten Stilund , Tove Christensen , Thor Petersen and Holger Jon Møller EMAIL logo

Abstract

Background

Detection of intrathecal immunoglobulin G (IgG) synthesis by gold standard oligoclonal bands (OCB) or IgG index remains an integral part of multiple sclerosis (MS) diagnostics, although both methods have weaknesses. Emerging evidence suggests that automated detection of free light chains (FLC) in the cerebrospinal fluid (CSF) has diagnostic performance equal to OCB. The objective of this study was to compare the diagnostic performance of CSF FLC with OCB and IgG index in a large cohort of Scandinavian patients referred for MS evaluation.

Methods

We prospectively included 230 patients suspected for MS. They are composed of patients with MS (n=96), clinically isolated syndrome (n=37), other neurological diseases (OND, n=31) and symptomatic controls (SC, n=66). CSF and serum samples were analyzed for kappa and lambda FLC, OCB and IgG index. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis.

Results

Both the absolute concentration of CSF-kappa and the kappa index had excellent MS diagnostic performances with ROC area under the curve of 0.93 and 0.94 (MS vs. SC+OND). At the 0.42 mg/L cutoff, CSF-kappa had sensitivity and specificity of 93.8% and 85.6%, whereas sensitivity and specificity for OCB was 82.3% and 93.8% (72.9% and 95.9% for IgG index at cutoff 0.64). CSF-lambda and lambda index performed inferior to CSF-kappa and kappa index.

Conclusions

CSF-kappa and kappa index represent automated, rapid and low-cost alternatives to OCB. Using merely the absolute concentration of CSF-kappa is a logistic advantage in the clinical laboratories.


Corresponding author: Prof. Holger Jon Møller, MD, PhD, Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark, Phone: 0045 31202201

Acknowledgments

We sincerely thank laboratory technicians Bodil L. Andersen and Inge Lund for excellent technical and logistic assistance.

  1. Author contributions: MC provided acquisition of data and statistical analysis, interpreted data, participated in study concept and design and drafted and finalized the manuscript. MCG and MS provided data collection. TC participated in study concept and design. TP provided data collection, interpreted data and participated in study concept and design. HJM provided acquisition of data, interpreted data, finalized the manuscript and led the development of the study concept and design. All authors read and approved the final manuscript. All authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The study was supported by the Danish Central Region, Department of Clinical Biochemistry. The Binding Site delivered kits for free light chains measurements free of charge. The company had no involvement in the study design, collection of samples, analysis and interpretation of data, writing of the report or decision to submit the article for publication.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organizations played no role in the study design, in the collection, analysis and interpretation of data; in writing the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2018-0400).


Received: 2018-04-18
Accepted: 2018-06-25
Published Online: 2018-07-28
Published in Print: 2018-12-19

©2019 Walter de Gruyter GmbH, Berlin/Boston

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