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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

Online
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1437-4331
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Volume 57, Issue 2

Issues

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
  • Department of Biomedicine, Aarhus University, Bartholin Building, Aarhus C, Denmark
  • Department of Neurology, Aarhus University Hospital, Aarhus C, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Tove Christensen / Thor Petersen / Holger Jon Møller
Published Online: 2018-07-28 | DOI: https://doi.org/10.1515/cclm-2018-0400

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.

This article offers supplementary material which is provided at the end of the article.

Keywords: clinically isolated syndrome; diagnostic performance; free light chains; kappa; multiple sclerosis; oligoclonal bands

References

  • 1.

    Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med 2018;378:169–80.CrossrefPubMedGoogle Scholar

  • 2.

    Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018;17:162–73.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 3.

    Freedman MS, Thompson EJ, Deisenhammer F, Giovannoni G, Grimsley G, Keir G, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol 2005;62:865–70.Google Scholar

  • 4.

    McLean BN, Luxton RW, Thompson EJ. A study of immunoglobulin G in the cerebrospinal fluid of 1007 patients with suspected neurological disease using isoelectric focusing and the Log IgG-Index. A comparison and diagnostic applications. Brain 1990;113(Pt 5):1269–89.CrossrefPubMedGoogle Scholar

  • 5.

    Franciotta D, Lolli F. Interlaboratory reproducibility of isoelectric focusing in oligoclonal band detection. Clin Chem 2007;53:1557–8.PubMedCrossrefGoogle Scholar

  • 6.

    Rudick RA, French CA, Breton D, Williams GW. Relative diagnostic value of cerebrospinal fluid kappa chains in MS: comparison with other immunoglobulin tests. Neurology 1989;39:964–8.PubMedCrossrefGoogle Scholar

  • 7.

    Krakauer M, Schaldemose Nielsen H, Jensen J, Sellebjerg F. Intrathecal synthesis of free immunoglobulin light chains in multiple sclerosis. Acta Neurol Scand 1998;98:161–5.CrossrefPubMedGoogle Scholar

  • 8.

    Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001;47:673–80.PubMedGoogle Scholar

  • 9.

    Desplat-Jego S, Feuillet L, Pelletier J, Bernard D, Cherif AA, Boucraut J. Quantification of immunoglobulin free light chains in cerebrospinal fluid by nephelometry. J Clin Immunol 2005;25:338–45.PubMedCrossrefGoogle Scholar

  • 10.

    Presslauer S, Milosavljevic D, Brucke T, Bayer P, Hubl W. Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis. J Neurol 2008;255:1508–14.CrossrefWeb of ScienceGoogle Scholar

  • 11.

    Duranti F, Pieri M, Centonze D, Buttari F, Bernardini S, Dessi M. Determination of kappaFLC and kappa Index in cerebrospinal fluid: a valid alternative to assess intrathecal immunoglobulin synthesis. J Neuroimmunol 2013;263:116–20.PubMedCrossrefGoogle Scholar

  • 12.

    Hassan-Smith G, Durant L, Tsentemeidou A, Assi LK, Faint JM, Kalra S, et al. High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis. J Neuroimmunol 2014;276:175–9.Web of SciencePubMedCrossrefGoogle Scholar

  • 13.

    Makshakov G, Nazarov V, Kochetova O, Surkova E, Lapin S, Evdoshenko E. Diagnostic and prognostic value of the cerebrospinal fluid concentration of immunoglobulin free light chains in clinically isolated syndrome with conversion to multiple sclerosis. PLoS One 2015;10:e0143375.Web of SciencePubMedCrossrefGoogle Scholar

  • 14.

    Presslauer S, Milosavljevic D, Huebl W, Aboulenein-Djamshidian F, Krugluger W, Deisenhammer F, et al. Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: a multicenter study. Mult Scler 2016;22:502–10.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 15.

    Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011;69:292–302.Web of ScienceCrossrefPubMedGoogle Scholar

  • 16.

    Miller DH, Chard DT, Ciccarelli O. Clinically isolated syndromes. Lancet Neurol 2012;11:157–69.Web of SciencePubMedCrossrefGoogle Scholar

  • 17.

    Granberg T, Martola J, Kristoffersen-Wiberg M, Aspelin P, Fredrikson S. Radiologically isolated syndrome – incidental magnetic resonance imaging findings suggestive of multiple sclerosis, a systematic review. Mult Scler 2013;19:271–80.CrossrefWeb of SciencePubMedGoogle Scholar

  • 18.

    Stilund M, Reuschlein AK, Christensen T, Moller HJ, Rasmussen PV, Petersen T. Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis. PLoS One 2014;9:e98588.CrossrefWeb of SciencePubMedGoogle Scholar

  • 19.

    Stilund M, Gjelstrup MC, Petersen T, Moller HJ, Rasmussen PV, Christensen T. Biomarkers of inflammation and axonal degeneration/damage in patients with newly diagnosed multiple sclerosis: contributions of the soluble CD163 CSF/serum ratio to a biomarker panel. PLoS One 2015;10:e0119681.Web of ScienceCrossrefPubMedGoogle Scholar

  • 20.

    Fortini AS, Sanders EL, Weinshenker BG, Katzmann JA. Cerebrospinal fluid oligoclonal bands in the diagnosis of multiple sclerosis. Isoelectric focusing with IgG immunoblotting compared with high-resolution agarose gel electrophoresis and cerebrospinal fluid IgG index. Am J Clin Pathol 2003;120:672–5.CrossrefGoogle Scholar

  • 21.

    Dobson R, Ramagopalan S, Davis A, Giovannoni G. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry 2013;84:909–14.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 22.

    Reiber H. Free light chains in CSF – pushing a method with biased interpretations. Acta Neurol Scand 2009;120:445–6; author reply 447–9.Web of ScienceCrossrefPubMedGoogle Scholar

About the article

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


Received: 2018-04-18

Accepted: 2018-06-25

Published Online: 2018-07-28

Published in Print: 2018-12-19


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.

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.

Employment or leadership: None declared.

Honorarium: None declared.

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.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 2, Pages 210–220, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2018-0400.

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