Deisenhammer F, Bartos A, Egg R, Gilhus NE, Giovannoni G, Rauer S, et al. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol 2006;13:913–22.PubMedCrossrefGoogle Scholar
Reiber H. Flow rate of cerebrospinal fluid (CSF) – a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 1994;122:189–203.CrossrefPubMedGoogle Scholar
Souverijn JH, Serrée HM, Peet R, Grenzebach Smit W, Bruyn GW. Intrathecal immunoglobulin synthesis. Comparison of various formulae with the “gold standard” of isoelectric focusing. J Neurol Sci 1991;102:11–6.PubMedGoogle Scholar
Ohman S, Ernerudh J, Forsberg P, Henriksson A, von Schenck H, Vrethem M. Comparison of seven formulae and isoelectrofocusing for determination of intrathecally produced IgG in neurological diseases. Ann Clin Biochem 1992;29 (Pt 4):405–10.PubMedCrossrefGoogle Scholar
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
Presslauer S, Milosavljevic D, Huebl W, Parigger S, Schneider-Koch G, Bruecke T. Kappa free light chains: diagnostic and prognostic relevance in MS and CIS. PLoS One 2014;9:e89945.Web of SciencePubMedCrossrefGoogle Scholar
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. J Neurol 2008;255:1508–14.CrossrefWeb of ScienceGoogle Scholar
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.Web of ScienceCrossrefPubMedGoogle Scholar
Hegen H, Milosavljevic D, Schnabl C, Manowiecka A, Walde J, Deisenhammer F, et al. Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis. Clin Chem Lab Med 2018;56:1383–91.Web of SciencePubMedCrossrefGoogle Scholar
Nakano T, Matsui M, Inoue I, Awata T, Katayama S, Murakoshi T. Free immunoglobulin light chain: its biology and implications in diseases. Clin Chim Acta 2011;412:843–9.Web of SciencePubMedCrossrefGoogle Scholar
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 ScienceCrossrefPubMedGoogle Scholar
Senel M, Tumani H, Lauda F, Presslauer S, Mojib-Yezdani R, Otto M, et al. Cerebrospinal fluid immunoglobulin kappa light chain in clinically isolated syndrome and multiple sclerosis. PLoS One 2014;9:e88680.Web of SciencePubMedCrossrefGoogle Scholar
Fischer C, Arneth B, Koehler J, Lotz J, Lackner KJ. Kappa free light chains in cerebrospinal fluid as markers of intrathecal immunoglobulin synthesis. Clin Chem 2004;50:1809–13.CrossrefPubMedGoogle Scholar
Zeman D, Kušnierová P, Bartoš V, Hradílek P, Kurková B, Zapletalová O. Quantitation of free light chains in the cerebrospinal fluid reliably predicts their intrathecal synthesis. Ann Clin Biochem 2016;53(Pt 1):174–6.CrossrefPubMedWeb of ScienceGoogle Scholar
Miller DH, Weinshenker BG, Filippi M, Banwell BL, Cohen JA, Freedman MS, et al. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Mult Scler 2008;14:1157–74.Web of ScienceCrossrefPubMedGoogle Scholar
Polman CH, Reingold SC, Edan G, Filippi M, Hartung H-P, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 2005;58:840–6.PubMedCrossrefGoogle Scholar
Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, et al. A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology 2009;73:1914–22.CrossrefWeb of SciencePubMedGoogle Scholar
Hoedemakers RM, Pruijt JF, Hol S, Teunissen E, Martens H, Stam P, et al. Clinical comparison of new monoclonal antibody-based nephelometric assays for free light chain kappa and lambda to polyclonal antibody-based assays and immunofixation electrophoresis. Clin Chem Lab Med 2011;50:489–95.PubMedGoogle Scholar
te Velthuis H, Knop I, Stam P, van den Broek M, Bos HK, Hol S, et al. N Latex FLC – new monoclonal high-performance assays for the determination of free light chain kappa and lambda. Clin Chem Lab Med 2011;49:1323–32.PubMedWeb of ScienceGoogle Scholar
Duranti F, Pieri M, Centonze D, Buttari F, Bernardini S, Dessi M. Determination of κFLC and κ Index in cerebrospinal fluid: a valid alternative to assess intrathecal immunoglobulin synthesis. J Neuroimmunol 2013;263:116–20.PubMedCrossrefGoogle Scholar
Christiansen M, Gjelstrup MC, Stilund M, Christensen T, Petersen T, Jon Møller H. Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis. Clin Chem Lab Med 2018;57:210–20.Web of ScienceCrossrefGoogle Scholar
Gurtner KM, Shosha E, Bryant SC, Andreguetto BD, Murray DL, Pittock SJ, et al. CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes. Clin Chem Lab Med 2018;56:1071–80.Web of SciencePubMedCrossrefGoogle Scholar
Puthenparampil M, Altinier S, Stropparo E, Zywicki S, Poggiali D, Cazzola C, et al. Intrathecal K free light chain synthesis in multiple sclerosis at clinical onset associates with local IgG production and improves the diagnostic value of cerebrospinal fluid examination. Mult Scler Relat Disord 2018;25:241–5.Web of SciencePubMedCrossrefGoogle Scholar
Valencia-Vera E, Martinez-Escribano Garcia-Ripoll A, Enguix A, Abalos-Garcia C, Segovia-Cuevas MJ. Application of κ free light chains in cerebrospinal fluid as a biomarker in multiple sclerosis diagnosis: development of a diagnosis algorithm. Clin Chem Lab Med 2018;56:609–13.PubMedCrossrefWeb of ScienceGoogle Scholar
Vasilj M, Kes VB, Vrkic N, Vukasovic I. Relevance of KFLC quantification to differentiate clinically isolated syndrome from multiple sclerosis at clinical onset. Clin Neurol Neurosurg 2018;174:220–9.CrossrefWeb of SciencePubMedGoogle Scholar
Menéndez-Valladares P, García-Sánchez MI, Cuadri Benítez P, Lucas M, Adorna Martínez M, Carranco Galán V, et al. Free kappa light chains in cerebrospinal fluid as a biomarker to assess risk conversion to multiple sclerosis. Mult Scler J Exp Transl Clin 2015;1:2055217315620935.PubMedGoogle Scholar
Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009;23:215–24.CrossrefWeb of ScienceGoogle Scholar
About the article
Published Online: 2019-05-21
Published in Print: 2019-09-25
Author contributions: H. Hegen participated in the conception and design of the study, acquisition and statistical analysis of the data, and in drafting the manuscript. J. Walde participated in statistical analysis of the data and in reviewing the manuscript for intellectual content. D. Milosavljevic participated in acquisition of the data and in reviewing the manuscript for intellectual content. F. Aboulenein-Djamshidian participated in acquisition of the data and in reviewing the manuscript for intellectual content. M. Senel participated in acquisition of the data and in reviewing the manuscript for intellectual content. H. Tumani participated in acquisition of the data and in reviewing the manuscript for intellectual content. F. Deisenhammer participated in reviewing the manuscript for intellectual content. S. Presslauer participated in the conception and design of the study, acquisition of the data, and in reviewing the manuscript for intellectual content. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Multiple Sclerosis Society Vienna. H. Hegen participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Merck, Novartis, Sanofi-Genzyme and Teva, and received honoraria for acting as consultant for Teva. M. Senel received honoraria for speaking and/or travel from Bayer, Biogen, Sanofi Genzyme and TEVA and research funding from the Hertha-Nathorff-Program and University of Ulm, none related to this study. H. Tumani received funding for research projects, lectures and travel from Bayer, Biogen, Genzyme, Fresenius, Merck, Mylan, Novartis, Roche, Siemens Health Diagnostics, Teva, and received research support from Hertie-Stiftung, BMBF, University of Ulm and Landesstiftung BW. F. Deisenhammer participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and Teva-Ratiopharm. His institution has received financial support for participation in randomized controlled trials of INFb-1b (Betaferon, Bayer Schering Pharma), INFb-1a (Avonex, Biogen; Rebif, Merck Serono), glatiramer acetate (Copaxone, Teva Pharmaceuticals), Natalizumab (Tysabri, Biogen), in multiple sclerosis. He is section editor of the MSARD journal (Multiple Sclerosis and Related Disorders). S. Presslauer participated in meetings sponsored by Bayer Schering, Biogen Idec, Merck Serono, Novartis and Teva.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.