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Free Kappa light chains in neuroinflammatory disorders: Complement rather than substitute?

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Bayart, Jean-Louis [UCL] Muls, Nathalie [UCL] Van Pesch, Vincent [UCL]

The detection of cerebrospinal fluid (CSF)-specific IgG oligoclonal bands (OCB) by isoelectric focusing (IEF) is widely used to help diagnose inflammatory neurological disorders (IND), including multiple sclerosis. However, the quantification of free light chains (FLC) is increasingly evaluated as a surrogate method to determine the presence of an intrathecal inflammatory process. The objective of this study was to evaluate the diagnostic performance of kappa (κ) FLC measurement in comparison with OCB detection by IEF. We measured serum and CSF κFLCs by turbidimetry using the SPA automated analyser and calculated the κ index in 142 samples from OCB-positive and negative MS, as well as from patients with inflammatory and non-inflammatory neurological disorders (IND and NIND). The κFLC index was significantly increased in OCB-positive MS and IND patients versus OCB-negative patients. Its performance was relatively comparable to that of IEF for MS diagnosis. When using a κFLC index cutoff value of 6.29, sensitivity increased from 61.2% to 75.7% in comparison with IEF for diagnosing IND (P = .0051), with a slightly lower non-statistically significant specificity (82.1% vs 100%). When considering both OCB status positivity or a κFLC index superior to 6.29 to diagnose IND status, sensitivity raised to 80.6% (P < .05) with an equal specificity. Our results demonstrate that the κFLC index does not discriminate MS from other IND patients, but is a reliable technique to detect intrathecal inflammation. However, κFLC quantification should probably be considered as a complementary method, rather than a substitute, to OCB detection.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2018
Language Anglais
Journal information "Acta neurologica Scandinavica" - Vol. 138, no. 4, p. 352-358 (2018)
Peer reviewed yes
e-issn 1600-0404
Publication status Publié
Affiliations UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
UCL - (SLuc) Service de neurologie
UCL - (SLuc) Service de biochimie médicale
Keywords cerebrospinal fluid ; free kappa light chains ; multiple sclerosis ; neuroinflammatory disorders ; oligoclonal bands
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  1. Polman Chris H., Reingold Stephen C., Banwell Brenda, Clanet Michel, Cohen Jeffrey A., Filippi Massimo, Fujihara Kazuo, Havrdova Eva, Hutchinson Michael, Kappos Ludwig, Lublin Fred D., Montalban Xavier, O'Connor Paul, Sandberg-Wollheim Magnhild, Thompson Alan J., Waubant Emmanuelle, Weinshenker Brian, Wolinsky Jerry S., Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria, 10.1002/ana.22366
  2. 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, 10.1136/jnnp-2012-304695
  3. von Büdingen Hans-Christian, Gulati Monica, Kuenzle Sandra, Fischer Katja, Rupprecht Tobias A., Goebels Norbert, Clonally expanded plasma cells in the cerebrospinal fluid of patients with central nervous system autoimmune demyelination produce “oligoclonal bands”, 10.1016/j.jneuroim.2009.10.005
  4. Cohen, Mult Scler J, 23, 8 (2017)
  5. Sindic C.J.M., Monteyne Ph., Laterre E.C., The intrathecal synthesis of virus-specific oligoclonal IgG in multiple sclerosis, 10.1016/0165-5728(94)90233-x
  6. Presslauer S., Milosavljevic D., Brücke T., Bayer P., Hübl W., Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis, 10.1007/s00415-008-0954-z
  7. Presslauer Stefan, Milosavljevic Dejan, Huebl Wolfgang, Aboulenein-Djamshidian Fahmy, Krugluger Walter, Deisenhammer Florian, Senel Makbule, Tumani Hayrettin, Hegen Harald, Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: A multicenter study, 10.1177/1352458515594044
  8. Presslauer Stefan, Milosavljevic Dejan, Huebl Wolfgang, Parigger Silvia, Schneider-Koch Gabriele, Bruecke Thomas, Kappa Free Light Chains: Diagnostic and Prognostic Relevance in MS and CIS, 10.1371/journal.pone.0089945
  9. Senel Makbule, Tumani Hayrettin, Lauda Florian, Presslauer Stefan, Mojib-Yezdani Rehaneh, Otto Markus, Brettschneider Johannes, Cerebrospinal Fluid Immunoglobulin Kappa Light Chain in Clinically Isolated Syndrome and Multiple Sclerosis, 10.1371/journal.pone.0088680
  10. Arneth B., Birklein F., High sensitivity of free lambda and free kappa light chains for detection of intrathecal immunoglobulin synthesis in cerebrospinal fluid, 10.1111/j.1600-0404.2008.01058.x
  11. Fischer C., Kappa Free Light Chains in Cerebrospinal Fluid as Markers of Intrathecal Immunoglobulin Synthesis, 10.1373/clinchem.2004.033977
  12. Duranti Fabio, Pieri Massimo, Centonze Diego, Buttari Fabio, Bernardini Sergio, Dessi Mariarita, Determination of kFLC and K Index in cerebrospinal fluid: A valid alternative to assessintrathecal immunoglobulin synthesis, 10.1016/j.jneuroim.2013.07.006
  13. Hassan-Smith G., Durant L., Tsentemeidou A., Assi L.K., Faint J.M., Kalra S., Douglas M.R., Curnow S.J., High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis, 10.1016/j.jneuroim.2014.08.003
  14. Krakauer M., Nielsen H. Schaldemose, Jensen J., Sellebjerg F., Intrathecal synthesis of free immunoglobulin light chains in multiple sclerosis, 10.1111/j.1600-0404.1998.tb07287.x
  15. Desplat-jégo Sophie, Feuillet Lionel, Pelletier Jean, Bernard Dominique, Chérif André Ali, Boucraut José, Quantification of Immunoglobulin Free Light Chains in CerebroSpinal Fluid by Nephelometry, 10.1007/s10875-005-5371-9
  16. Teunissen C. E., Petzold A., Bennett J. L., Berven F. S., Brundin L., Comabella M., Franciotta D., Frederiksen J. L., Fleming J. O., Furlan R., Hintzen, MD R. Q., Hughes S. G., Johnson M. H., Krasulova E., Kuhle J., Magnone M. C., Rajda C., Rejdak K., Schmidt H. K., van Pesch V., Waubant E., Wolf C., Giovannoni G., Hemmer B., Tumani H., Deisenhammer F., A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking, 10.1212/wnl.0b013e3181c47cc2
  17. Teunissen Charlotte, Menge Til, Altintas Ayse, Álvarez-Cermeño José C, Bertolotto Antonio, Berven Frode S, Brundin Lou, Comabella Manuel, Degn Matilde, Deisenhammer Florian, Fazekas Franz, Franciotta Diego, Frederiksen Jette L, Galimberti Daniela, Gnanapavan Sharmilee, Hegen Harald, Hemmer Bernhard, Hintzen Rogier, Hughes Steve, Iacobaeus Ellen, Kroksveen Ann C, Kuhle Jens, Richert John, Tumani Hayrettin, Villar Luisa M, Drulovic Jelena, Dujmovic Irena, Khalil Michael, Bartos Ales, Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis, 10.1177/1352458513488232
  18. Sindic C.J.M., Laterre E.C., Oligoclonal free kappa and lambda bands in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases, 10.1016/0165-5728(91)90035-6
  19. Gastaldi Matteo, Zardini Elisabetta, Leante Rosaria, Ruggieri Maddalena, Costa Gianna, Cocco Eleonora, De Luca Giovanna, Cataldo Ivana, Biagioli Tiziana, Ballerini Clara, Castellazzi Massimiliano, Fainardi Enrico, Pettini Paola, Zaffaroni Mauro, Giunti Debora, Capello Elisabetta, Bernardi Gaetano, Ciusani Emilio, Giannotta Claudia, Nobile-Orazio Eduardo, Bazzigaluppi Elena, Passerini Gabriella, Bedin Roberta, Sola Patrizia, Brivio Rinaldo, Cavaletti Guido, Sala Arianna, Bertolotto Antonio, Desina Gaetano, Leone Maurizio A., Mariotto Sara, Ferrari Sergio, Paternoster Andreina, Giavarina Davide, Lolli Francesco, Franciotta Diego, Cerebrospinal fluid analysis and the determination of oligoclonal bands, 10.1007/s10072-017-3034-2
  20. Trajman A., Luiz R. R., McNemar χ2test revisited: comparing sensitivity and specificity of diagnostic examinations, 10.1080/00365510701666031
  21. Apostolski S., Nikolić J., Bugarski-Prokopljević C., Miletić V., Pavlović S., Filipović S., Serum and CSF immunological findings in ALS, 10.1111/j.1600-0404.1991.tb04656.x
  22. Tate Jillian R., Mollee Peter, Dimeski Goce, Carter Andrew C., Gill Devinder, Analytical performance of serum free light-chain assay during monitoring of patients with monoclonal light-chain diseases, 10.1016/j.cca.2006.07.011
  23. Tate, Clin Biochem Rev, 30, 131 (2009)
  24. Villar Luisa M., Espiño Mercedes, Costa-Frossard Lucienne, Muriel Alfonso, Jiménez Juana, Álvarez-Cermeño José C., High levels of cerebrospinal fluid free kappa chains predict conversion to multiple sclerosis, 10.1016/j.cca.2012.07.007
  25. Reiber Hansotto, Free light chains in CSF - pushing a method with biased interpretations : Letter to the editor, 10.1111/j.1600-0404.2009.01244.x
  26. Tate, Clin Biochem Rev, 30, 89 (2009)
  27. Petzold Axel, Intrathecal oligoclonal IgG synthesis in multiple sclerosis, 10.1016/j.jneuroim.2013.06.014
  28. Goffette S, Detection of oligoclonal free kappa chains in the absence of oligoclonal IgG in the CSF of patients with suspected multiple sclerosis, 10.1136/jnnp.2003.010710
  29. Zeman David, Kušnierová Pavlína, Švagera Zdeněk, Všianský František, Byrtusová Monika, Hradílek Pavel, Kurková Barbora, Zapletalová Olga, Bartoš Vladimír, Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting, 10.1371/journal.pone.0166556
  30. Crespi Ilaria, Sulas Maria, Mora Riccardo, Naldi Paola, Vecchio Domizia, Comi Cristoforo, Cantello Roberto, Bellomo Giorgio, Combined use of Kappa Free Light Chain Index and Isoelectrofocusing of Cerebro-Spinal Fluid in Diagnosing Multiple Sclerosis: Performances and Costs, 10.7754/clin.lab.2016.160930
Bibliographic reference Bayart, Jean-Louis ; Muls, Nathalie ; Van Pesch, Vincent. Free Kappa light chains in neuroinflammatory disorders: Complement rather than substitute?. In: Acta neurologica Scandinavica, Vol. 138, no. 4, p. 352-358 (2018)
Permanent URL http://hdl.handle.net/2078.1/202575