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Cited by 47Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersClinical Laboratory Practices and Quality Control

The increasing role of Kappa free light chains in the diagnosis of multiple sclerosis

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Konen, Franz Felix, Schwenkenbecher, Philipp, Jendretzky, Konstantin Fritz, Gingele, Stefan, Sühs, Kurt-Wolfram, Tumani, Hayrettin, Süße, Marie, Skripuletz, Thomas·2021·Cells
DOI 10.3390/cells10113056PMC PMC8622045
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Abstract

Free light chains (FLC) are a promising biomarker to detect intrathecal inflammation in patients with inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). The diagnostic use of this biomarker, in particular the kappa isoform of FLC (“KFLC”), has been investigated for more than 40 years. Based on an extensive literature review, we found that an agreement on the correct method for evaluating KFLC concentrations has not yet been reached. KFLC indices with varying cut-off values and blood-CSF-barrier (QAlbumin) related non-linear formulas for KFLC interpretation have been investigated in several studies. All approaches revealed high diagnostic sensitivity and specificity compared with the oligoclonal bands, which are considered the gold standard for the detection of intrathecally synthesized immunoglobulins. Measurement of KFLC is fully automated, rater-independent, and has been shown to be stable against most pre-analytic influencing factors. In conclusion, the determination of KFLC represents a promising diagnostic approach to show intrathecal inflammation in neuroinflammatory diseases. Multicenter studies are needed to show the diagnostic sensitivity and specificity of KFLC in MS by using the latest McDonald criteria and appropriate, as well as standardized, cut-off values for KFLC concentrations, preferably considering non-linear formulas such as Reiber’s diagram.

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  • CSF analysis in general and detection of CSF-restricted oligoclonal bands in special are pivotal for differential diagnosis beyond the diagnostic contribution, helping to exclude mimics and provide additional diagnostic information such as the clonality of IgG.

    “CSF analysis in general and detection of CSF-restricted oligoclonal bands in special are pivotal for differential diagnosis beyond the diagnostic contribution, helping to exclude mimics and provide additional diagnostic information such as the clonality of IgG.”

    From Applying the 2024-revised McDonald criteria for multiple sclerosis using conventional diagnostic tools: a single-centre prospective cohort study in Germany (2026) · cites this paper as [36]

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  1. [1]Bollengier F. Lowenthal A. Henrotin W. Bound and free light chains in subacute sclerosing panencephalitis and multiple sclerosis serum and cerebrospinal fluid Z. Klin. Chem. Klin. Biochem. 1975 13 305 310 10.1515/cclm.1975.13.7.305 810984 · DOI
  2. [2]Solomon A. Bence-Jones proteins and light chains of immunoglobulins (second of two parts) N. Engl. J. Med. 1976 294 91 98 10.1056/NEJM197601082940206 53788 · DOI
  3. [3]Kaplan B. Livneh A. Sela B.A. Immunoglobulin free light chain dimers in human diseases TheScientificWorldJournal 2011 11 726 735 10.1100/tsw.2011.65 PMC5720091 21442150 · DOI
  4. [4]Stendahl-Brodin L. Link H. Relation between benign course of multiple sclerosis and low-grade humoral immune response in cerebrospinal fluid J. Neurol. Neurosurg. Psychiatry 1980 43 102 105 10.1136/jnnp.43.2.102 7359146 PMC490482 · DOI
  5. [5]Reich D.S. Lucchinetti C.F. Calabresi P.A. Multiple Sclerosis N. Engl. J. Med. 2018 378 169 180 10.1056/NEJMra1401483 29320652 PMC6942519 · DOI · Paper page
  6. [6]Cerqueira J.J. Compston D.A.S. Geraldes R. Rosa M.M. Schmierer K. Thompson A. Tinelli M. Palace J. Time matters in multiple sclerosis: Can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis? J. Neurol. Neurosurg. Psychiatry 2018 89 844 850 10.1136/jnnp-2017-317509 29618493 PMC6204938 · DOI
  7. [7]Comi G. Martinelli V. Rodegher M. Moiola L. Bajenaru O. Carra A. Elovaara I. Fazekas F. Hartung H. Hillert J. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): A randomised, double-blind, placebo-controlled trial Lancet 2009 374 1503 1511 10.1016/S0140-6736(09)61259-9 19815268 · DOI
  8. [8]Kappos L. Polman C.H. Freedman M.S. Edan G. Hartung H.P. Miller D.H. Montalban X. Barkhof F. Bauer L. Jakobs P. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes Neurology 2006 67 1242 1249 10.1212/01.wnl.0000237641.33768.8d 16914693 · DOI
  9. [9]Tintore M. Rovira À. Río J. Otero-Romero S. Arrambide G. Tur C. Comabella M. Nos C. Arevalo M.J. Negrotto L. Defining high, medium and low impact prognostic factors for developing multiple sclerosis Brain 2015 138 Pt 7 1863 1874 10.1093/brain/awv105 25902415 · DOI · Paper page
  10. [11]Schumacher G.A. Beebe G. Kibler R.F. Kurland L.T. Kurtzke J.F. McDowell F. Nagler B. Sibley W.A. Tourtellotte W.W. Willmon T.L. Problems of experimental trials of therapy in multiple sclerosis: Report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis Ann. N. Y. Acad. Sci. 1965 122 552 568 10.1111/j.1749-6632.1965.tb20235.x 14313512 · DOI · Paper page
  11. [12]Poser C.M. Paty D.W. Scheinberg L. McDonald W.I. Davis F.A. Ebers G.C. Johnson K.P. Sibley W.A. Silberberg D.H. Tourtellotte W.W. New diagnostic criteria for multiple sclerosis: Guidelines for research protocols Ann. Neurol. 1983 13 227 231 10.1002/ana.410130302 6847134 · DOI · Paper page
  12. [13]McDonald W.I. Compston A. Edan G. Goodkin D. Hartung H.-P. Lublin F.D. McFarland H.F. Paty D.W. Polman C.H. Reingold S.C. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis Ann. Neurol. 2001 50 121 127 10.1002/ana.1032 11456302 · DOI · Paper page
  13. [14]Polman C.H. Reingold S.C. Edan G. Filippi M. Hartung H.-P. Kappos L. Lublin F.D. Metz L.M. McFarland H.F. O’Connor P.W. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria” Ann. Neurol. 2005 58 840 846 10.1002/ana.20703 16283615 · DOI · Paper page
  14. [15]Polman C.H. Reingold S.C. Banwell B. Clanet M. Cohen J.A. Filippi M. Fujihara K. Havrdova E. Hutchinson M. Kappos L. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria Ann. Neurol. 2011 69 292 302 10.1002/ana.22366 21387374 PMC3084507 · DOI · Paper page
  15. [16]Thompson A.J. Banwell B.L. Barkhof F. Carroll W.M. Coetzee T. Comi G. Correale J. Fazekas F. Filippi M. Freedman M.S. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria Lancet Neurol. 2018 17 162 173 10.1016/S1474-4422(17)30470-2 29275977 · DOI · Paper page
  16. [17]Andersson M. Alvarez-Cermeño J. Bernardi G. Cogato I. Fredman P. Frederiksen J. Fredrikson S. Gallo P. Grimaldi L.M. Gronning M. Cerebrospinal fluid in the diagnosis of multiple sclerosis: A consensus report J. Neurol. Neurosurg. Psychiatry 1994 57 897 902 10.1136/jnnp.57.8.897 8057110 PMC1073070 · DOI · Paper page
  17. [18]Presslauer S. Milosavljevic D. Huebl W. Aboulenein-Djamshidian F. Krugluger W. Deisenhammer F. Senel M. Tumani H. Hegen H. Validation of kappa free light chains as a diagnostic biomarker in multiple sclerosis and clinically isolated syndrome: A multicenter study Mult. Scler. J. 2016 22 502 510 10.1177/1352458515594044 26199348 · DOI
  18. [19]Zeman D. Kušnierová P. Švagera Z. Všianský F. Byrtusová M. Hradílek P. Kurková B. Zapletalová O. Bartoš V. 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 PLoS ONE 2016 11 e0166556 10.1371/journal.pone.0166556 27846293 PMC5112955 · DOI
  19. [20]Emersic A. Anadolli V. Krsnik M. Rot U. Intrathecal immunoglobulin synthesis: The potential value of an adjunct test Clin. Chim. Acta 2019 489 109 116 10.1016/j.cca.2018.12.006 30529605 · DOI
  20. [21]Crespi I. Sulas M.G. Mora R. Naldi P. Vecchio D. Comi C. Cantello R. Bellomo G. Combined use of Kappa Free Light Chain Index and Isoelectrofocusing of Cerebro-Spinal Fluid in Diagnosing Multiple Sclerosis: Performances and Costs Clin. Lab 2017 63 551 559 10.7754/Clin.Lab.2016.160930 28271695 · DOI
  21. [22]Valencia-Vera E. Martinez-Escribano Garcia-Ripoll A. Enguix A. Abalos-Garcia C. Segovia-Cuevas M.J. 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 56 609 613 10.1515/cclm-2017-0285 29087953 · DOI
  22. [23]Gurtner K.M. Shosha E. Bryant S.C. Andreguetto B.D. Murray D.L. Pittock S.J. Willrich M.A.V. CSF free light chain identification of demyelinating disease: Comparison with oligoclonal banding and other CSF indexes Clin. Chem. Lab. Med. 2018 56 1071 1080 10.1515/cclm-2017-0901 29455184 · DOI
  23. [24]Schwenkenbecher P. Konen F.F. Wurster U. Witte T. Gingele S. Sühs K.-W. Stangel M. Skripuletz T. Reiber’s Diagram for Kappa Free Light Chains: The New Standard for Assessing Intrathecal Synthesis? Diagnostics 2019 9 194 10.3390/diagnostics9040194 31744096 PMC6963502 · DOI
  24. [25]Reiber H. Zeman D. Kušnierová P. Mundwiler E. Bernasconi L. Diagnostic relevance of free light chains in cerebrospinal fluid—The hyperbolic reference range for reliable data interpretation in quotient diagrams Clin. Chim. Acta 2019 497 153 162 10.1016/j.cca.2019.07.027 31351929 · DOI
  25. [26]Süße M. Feistner F. Grothe M. Nauck M. Dressel A. Hannich M.J. Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy Neurol. Neuroimmunol. Neuroinflamm. 2020 7 e892 10.1212/NXI.0000000000000892 32948648 PMC7524577 · DOI
  26. [27]Konen F.F. Wurster U. Witte T. Jendretzky K.F. Gingele S. Tumani H. Sühs K.-W. Stangel M. Schwenkenbecher P. Skripuletz T. The Impact of Immunomodulatory Treatment on Kappa Free Light Chains as Biomarker in Neuroinflammation Cells 2020 9 842 10.3390/cells9040842 32244362 PMC7226742 · DOI
  27. [28]Süße M. Reiber H. Grothe M. Petersmann A. Nauck M. Dressel A. Hannich M.J. Free light chain kappa and the polyspecific immune response in MS and CIS—Application of the hyperbolic reference range for most reliable data interpretation J. Neuroimmunol. 2020 346 577287 10.1016/j.jneuroim.2020.577287 32599341 · DOI
  28. [29]Süße M. Feistner F. Holbe C. Grothe M. Nauck M. Dressel A. Hannich M.J. Diagnostic value of kappa free light chains in patients with one isolated band in isoelectric focusing Clin. Chim. Acta 2020 507 205 209 10.1016/j.cca.2020.04.029 32353362 · DOI
  29. [31]Stangel M. Fredrikson S. Meinl E. Petzold A. Stüve O. Tumani H. The utility of cerebrospinal fluid analysis in patients with multiple sclerosis Nat. Rev. Neurol. 2013 9 267 276 10.1038/nrneurol.2013.41 23528543 · DOI · Paper page
  30. [32]Wurster U. Elektrophoreseverfahren—Nachweis und Bedeutung von oligoklonalen Banden Klinische Liquordiagnostik 2nd ed. Zettl U.K. Lehmitz R. Mix E. De Gruyter Berlin, Germany New York, NY, USA 2009 208 234
  31. [33]Duell F. Evertsson B. Al Nimer F. Sandin Å. Olsson D. Olsson T. Khademi M. Hietala M.A. Piehl F. Hansson M. Diagnostic accuracy of intrathecal kappa free light chains compared with OCBs in MS Neurol. Neuroimmunol. Neuroinflamm. 2020 7 e775 10.1212/NXI.0000000000000775 32527760 PMC7309528 · DOI
  32. [34]Olsson T. Kostulas V. Link H. Improved detection of oligoclonal IgG in cerebrospinal fluid by isoelectric focusing in agarose, double-antibody peroxidase labeling, and avidin-biotin amplification Clin. Chem. 1984 30 1246 1249 10.1093/clinchem/30.7.1246 6375900 · DOI
  33. [35]Wurster U. Demonstration of Oligoclonal IgG in the unconcentrated CSF by silver stain Electrophoresis ′82 Stathakos D. De Gruyter Berlin, Germany New York, NY, USA 1983 250 259
  34. [36]Wurster U. Haas J. Patzold U. Cerebrospinal fluid findings in isolated optic neuritis Fortschr. Ophthalmol. 1983 80 35 38 6350131
  35. [38]Coyle P.K. Johnson C. Optimal detection of oligoclonal bands in CSF by silver stain Neurology 1983 33 1510 1512 10.1212/WNL.33.11.1510 6195553 · DOI
  36. [39]Rammohan K.W. Oligoclonal bands in unconcentrated CSF. Silver stain for agarose gels Neurochem. Pathol. 1985 3 15 25 10.1007/BF02834072 2410821 · DOI
  37. [40]Mehta P.D. Patrick B.A. Black J. Detection of oligoclonal IgG bands in unconcentrated CSF by isoelectric focusing in agarose gel and silver staining J. Neurosci. Methods 1986 16 277 282 10.1016/0165-0270(86)90052-X 2426528 · DOI
  38. [41]Radosavljević B. Agarose isoelectric focusing, antiserum immunofixation and silver staining for detection of oligoclonal bands in unconcentrated cerebrospinal fluid Acta Neurol. Scand. 1986 73 208 212 10.1111/j.1600-0404.1986.tb03265.x 2422867 · DOI
  39. [42]Schwenkenbecher P. Konen F.F. Wurster U. Jendretzky K.F. Gingele S. Sühs K.-W. Pul R. Witte T. Stangel M. Skripuletz T. The Persisting Significance of Oligoclonal Bands in the Dawning Era of Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis Int. J. Mol. Sci. 2018 19 3796 10.3390/ijms19123796 30501024 PMC6320811 · DOI
  40. [43]Rosenstein I. Rasch S. Axelsson M. Novakova L. Blennow K. Zetterberg H. Lycke J. Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real-world investigation J. Neurochem. 2021 10.1111/jnc.15500 34478561 · DOI
  41. [44]Gudowska-Sawczuk M. Tarasiuk J. Kułakowska A. Kochanowicz J. Mroczko B. Kappa Free Light Chains and IgG Combined in a Novel Algorithm for the Detection of Multiple Sclerosis Brain Sci. 2020 10 324 10.3390/brainsci10060324 32471086 PMC7349504 · DOI
  42. [45]Gaetani L. Di Carlo M. Brachelente G. Valletta F. Eusebi P. Mancini A. Gentili L. Borrelli A. Calabresi P. Sarchielli P. Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis J. Neuroimmunol. 2020 339 577108 10.1016/j.jneuroim.2019.577108 31743879 · DOI
  43. [46]Ferraro D. Trovati A. Bedin R. Natali P. Franciotta D. Santangelo M. Camera V. Vitetta F. Varani M. Trenti T. Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band-negative patients with suspected multiple sclerosis Eur. J. Neurol. 2020 27 461 467 10.1111/ene.14121 31710409 · DOI
  44. [47]Huss A. Mojib-Yezdani F. Bachhuber F. Fangerau T. Lewerenz J. Otto M. Tumani H. Senel M. Association of cerebrospinal fluid kappa free light chains with the intrathecal polyspecific antiviral immune response in multiple sclerosis Clin. Chim. Acta 2019 498 148 153 10.1016/j.cca.2019.08.016 31437445 · DOI
  45. [48]Altinier S. Puthenparampil M. Zaninotto M. Toffanin E. Ruggero S. Gallo P. Plebani M. Free light chains in cerebrospinal fluid of multiple sclerosis patients negative for IgG oligoclonal bands Clin. Chim. Acta 2019 496 117 120 10.1016/j.cca.2019.06.016 31233736 · DOI
  46. [49]Leurs C.E. Twaalfhoven H. Lissenberg-Witte B.I. Van Pesch V. Dujmovic I. Drulovic J. Castellazzi M. Bellini T. Pugliatti M. Kuhle J. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study Mult. Scler. 2020 26 912 923 10.1177/1352458519845844 31066634 PMC7350201 · DOI
  47. [50]Hegen H. Walde J. Milosavljevic D. Aboulenein-Djamshidian F. Senel M. Tumani H. Deisenhammer F. Presslauer S. Free light chains in the cerebrospinal fluid. Comparison of different methods to determine intrathecal synthesis Clin. Chem. Lab. Med. 2019 57 1574 1586 10.1515/cclm-2018-1300 31112501 · DOI
  48. [51]Senel M. Mojib-Yezdani F. Braisch U. Bachhuber F. Lewerenz J. Ludolph A.C. Otto M. Tumani H. CSF Free Light Chains as a Marker of Intrathecal Immunoglobulin Synthesis in Multiple Sclerosis: A Blood-CSF Barrier Related Evaluation in a Large Cohort Front. Immunol. 2019 10 641 10.3389/fimmu.2019.00641 30984199 PMC6449445 · DOI
  49. [52]Rathbone E. Durant L. Kinsella J. Parker A.R. Hassan-Smith G. Douglas M.R. Curnow S.J. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis J. Neurol. Neurosurg. Psychiatry 2018 89 1044 1049 10.1136/jnnp-2018-317947 29743290 PMC6166608 · DOI
  50. [53]Nazarov V.D. Makshakov G.S. Mazing A.V. Surkova E. Krasnov V.S. Shumilina M.V. Totolyan N.A. Evdoshenko E.P. Lapin S.V. Emanuel V.L. Diagnostic value of immunoglobulin free light chains at the debut of multiple sclerosis Zhurnal Nevrol. Psikhiatrii Im. SS Korsakova 2017 117 60 65 10.17116/jnevro20171172260-65 28617363 · DOI
  51. [54]Christiansen M. Gjelstrup M.C. 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 57 210 220 10.1515/cclm-2018-0400 30055097 · DOI
  52. [55]Sáez M.S. Rojas J.I. Lorenzón M.V. Sanchez F. Patrucco L. Míguez J. Azcona C. Sorroche P. Cristiano E. Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: Prospective cohort study in Buenos Aires J. Neurol. 2019 266 112 118 10.1007/s00415-018-9106-2 30386877 · DOI
  53. [56]Puthenparampil M. Altinier S. Stropparo E. Zywicki S. Poggiali D. Cazzola C. Toffanin E. Ruggero S. Grassivaro F. Zaninotto M. 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 25 241 245 10.1016/j.msard.2018.08.002 30130707 · DOI
  54. [57]Pieri M. Storto M. Pignalosa S. Zenobi R. Buttari F. Bernardini S. Centonze D. Dessi M. KFLC Index utility in multiple sclerosis diagnosis: Further confirmation J. Neuroimmunol. 2017 309 31 33 10.1016/j.jneuroim.2017.05.007 28601282 · DOI
  55. [58]Voortman M.M. Stojakovic T. Pirpamer L. Jehna M. Langkammer C. Scharnagl H. Reindl M. Ropele S. Seifert-Held T. Archelos J.-J. Prognostic value of free light chains lambda and kappa in early multiple sclerosis Mult. Scler. 2017 23 1496 1505 10.1177/1352458516681503 27899552 · DOI
  56. [59]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 1 174 176 10.1177/0004563215579110 25753032 · DOI
  57. [60]Passerini G. Dalla Costa G. Sangalli F. Moiola L. Colombo B. Locatelli M. Comi G. Furlan R. Martinelli V. Free Light Chains and Intrathecal B Cells Activity in Multiple Sclerosis: A Prospective Study and Meta-Analysis Mult. Scler. Int. 2016 2016 2303857 10.1155/2016/2303857 28116160 PMC5225376 · DOI
  58. [61]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 10.1371/journal.pone.0143375 26606531 PMC4659555 · DOI
  59. [62]Hassan-Smith G. Durant L. Tsentemeidou A. Assi L. Faint J. Kalra S. Douglas M. Curnow S. High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis J. Neuroimmunol. 2014 276 175 179 10.1016/j.jneuroim.2014.08.003 25146968 · DOI
  60. [63]Dobson R. Topping J. Davis A. Thompson E. Giovannoni G. Cerebrospinal fluid and urinary biomarkers in multiple sclerosis Acta Neurol. Scand. 2013 128 321 327 10.1111/ane.12119 23465040 · DOI
  61. [65]Arneth B. Birklein F. High sensitivity of free lambda and free kappa light chains for detection of intrathecal immunoglobulin synthesis in cerebrospinal fluid Acta Neurol. Scand. 2009 119 39 44 10.1111/j.1600-0404.2008.01058.x 18573131 · DOI
  62. [66]Presslauer S. Milosavljevic D. Brücke T. Bayer P. Hübl W. Elevated levels of kappa free light chains in CSF support the diagnosis of multiple J. Neurol. 2008 255 1508 1514 10.1007/s00415-008-0954-z 18685917 · DOI
  63. [67]Rudick R.A. Medendorp S.V. Namey M. Boyle S. Fischer J. Multiple sclerosis progression in a natural history study: Predictive value of cerebrospinal fluid free kappa light chains Mult. Scler. 1995 1 150 155 10.1177/135245859500100303 9345445 · DOI
  64. [68]Vecchio D. Bellomo G. Serino R. Virgilio E. Lamonaca M. Dianzani U. Cantello R. Comi C. Crespi I. Intrathecal kappa free light chains as markers for multiple sclerosis Sci. Rep. 2020 10 20329 10.1038/s41598-020-77029-7 33230241 PMC7683527 · DOI
  65. [69]Berek K. Bsteh G. Auer M. Di Pauli F. Grams A. Milosavljevic D. Poskaite P. Schnabl C. Wurth S. Zinganell A. Kappa-Free Light Chains in CSF Predict Early Multiple Sclerosis Disease Activity Neurol. Neuroimmunol. Neuroinflamm. 2021 8 e1005 10.1212/NXI.0000000000001005 34049994 PMC8168046 · DOI
  66. [70]Agnello L. Lo Sasso B. Salemi G. Altavilla P. Pappalardo E.M. Caldarella R. Meli F. Scazzone C. Bivona G. Ciaccio M. Clinical Use of κ Free Light Chains Index as a Screening Test for Multiple Sclerosis Lab. Med. 2020 51 402 407 10.1093/labmed/lmz073 31943078 · DOI
  67. [71]Cavalla P. Caropreso P. Limoncelli S. Bosa C. Pasanisi M. Schillaci V. Alteno A. Costantini G. Giordana M. Mengozzi G. Kappa free light chains index in the differential diagnosis of Multiple Sclerosis from Neuromyelitis optica spectrum disorders and other immune-mediated central nervous system disorders J. Neuroimmunol. 2020 339 577122 10.1016/j.jneuroim.2019.577122 31837636 · DOI
  68. [72]Vecchio D. Crespi I. Virgilio E. Naldi P. Campisi M. Serino R. Dianzani U. Bellomo G. Cantello R. Comi C. Kappa free light chains could predict early disease course in multiple sclerosis Mult. Scler. Relat. Disord. 2019 30 81 84 10.1016/j.msard.2019.02.001 30738877 · DOI
  69. [73]Vasilj M. Kes V.B. Vrkic N. Vukasovic I. Relevance of KFLC quantification to differentiate clinically isolated syndrome from multiple sclerosis at clinical onset Clin. Neurol. Neurosurg. 2018 174 220 229 10.1016/j.clineuro.2018.09.031 30278299 · DOI
  70. [74]Crespi I. Vecchio D. Serino R. Saliva E. Virgilio E. Sulas M.G. Bellomo G. Dianzani U. Cantello R. Comi C. K Index is a Reliable Marker of Intrathecal Synthesis, and an Alternative to IgG Index in Multiple Sclerosis Diagnostic Work-Up J. Clin. Med. 2019 8 446 10.3390/jcm8040446 30987052 PMC6518364 · DOI
  71. [75]Ferraro D. Bedin R. Natali P. Franciotta D. Smolik K. Santangelo M. Immovilli P. Camera V. Vitetta F. Gastaldi M. Kappa Index Versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders Diagnostics 2020 10 856 10.3390/diagnostics10100856 PMC7589948 33096861 · DOI
  72. [76]Salavisa M. Paixão P. Ladeira A.F. Mendes A. Correia A.S. Viana J.F. Baptista M.V. Prognostic value of kappa free light chains determination in first-ever multiple sclerosis relapse J. Neuroimmunol. 2020 347 577355 10.1016/j.jneuroim.2020.577355 32795735 · DOI
  73. [77]Rudick R.A. Cookfair D.L. Simonian N.A. Ransohoff R.M. Richert J.R. Jacobs L.D. Herndon R.M. Salazar A.M. Fischer J.S. Granger C.V. Cerebrospinal fluid abnormalities in a phase III trial of Avonex (IFNbeta-1a) for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group J. Neuroimmunol. 1999 93 8 14 10.1016/S0165-5728(98)00174-X 10378864 · DOI
  74. [78]Bayart J.L. Muls N. van Pesch V. Free Kappa light chains in neuroinflammatory disorders: Complement rather than substitute? Acta Neurol. Scand. 2018 138 352 358 10.1111/ane.12969 29900542 · DOI
  75. [79]Menéndez-Valladares P. García-Sánchez M.I. Martínez M.A. De Veas Silva J.L.G. Guitarte C.B. Ayuso G.I. Validation and meta-analysis of kappa index biomarker in multiple sclerosis diagnosis Autoimmun. Rev. 2019 18 43 49 10.1016/j.autrev.2018.07.010 30408586 · DOI
  76. [80]Süße M. Hannich M. Petersmann A. Zylla S. Pietzner M. Nauck M. Dressel A. Kappa free light chains in cerebrospinal fluid to identify patients with oligoclonal bands Eur. J. Neurol. 2018 25 1134 1139 10.1111/ene.13667 29683546 · DOI
  77. [81]Pieri M. Zenobi R. Morello M. Buttari F. Centonze D. Bernardini S. Dessi M. Multiple Sclerosis: kFLC index values related to gender Mult. Scler. Relat. Disord. 2018 26 58 60 10.1016/j.msard.2018.08.018 30223231 · DOI
  78. [82]Menéndez-Valladares P. García-Sánchez M.I. Benítez P.C. Lucas M. Martínez M.A. Galán V.C. Silva J.L.G.D.V. Guitarte C.B. Ayuso G.I. 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 10.1177/2055217315620935 28607709 PMC5433434 · DOI
  79. [83]Senel M. Tumani H. Lauda F. Presslauer S. Mojib-Yezdani R. Otto M. Brettschneider J. Cerebrospinal fluid immunoglobulin kappa light chain in clinically isolated syndrome and multiple sclerosis PLoS ONE 2014 9 e88680 10.1371/journal.pone.0088680 24695382 PMC3973621 · DOI
  80. [84]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 10.1371/journal.pone.0089945 24651567 PMC3940961 · DOI
  81. [85]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 263 116 120 10.1016/j.jneuroim.2013.07.006 23916392 · DOI
  82. [86]Villar L.M. Espiño M. Costa-Frossard L. Muriel A. Jiménez J. Alvarez-Cermeño J.C. High levels of cerebrospinal fluid free kappa chains predict conversion to multiple sclerosis Clin. Chim. Acta. 2012 413 1813 1816 10.1016/j.cca.2012.07.007 22814197 · DOI
  83. [87]Desplat-Jégo S. Feuillet L. Pelletier J. Bernard D. Chérif A.A. Boucraut J. Quantification of immunoglobulin free light chains in cerebrospinal fluid by nephelometry J. Clin. Immunol. 2005 25 338 345 10.1007/s10875-005-5371-9 16133990 · DOI
  84. [88]Fischer C. Arneth B. Koehler J. Lotz J. Lackner K.J. Kappa free light chains in cerebrospinal fluid as markers of intrathecal immunoglobulin synthesis Clin. Chem. 2004 50 1809 1813 10.1373/clinchem.2004.033977 15271859 · DOI
  85. [89]Lolli F. Siracusa G. Amato M.P. Fratiglioni L. Pozzo G.D. Galli E. Amaducci L. Intrathecal synthesis of free immunoglobulin light chains and IgM in initial multiple sclerosis Acta Neurol. Scand. 1991 83 239 243 10.1111/j.1600-0404.1991.tb04689.x 1904673 · DOI
  86. [90]Lolli F. Amaducci L. Measurement of free kappa immunoglobulin light chains in the cerebrospinal fluid by a competitive avidin-biotin ELISA Clin. Chim. Acta 1989 182 229 234 10.1016/0009-8981(89)90081-8 2505952 · DOI
  87. [91]Allal C. Ghaffor M. Rabhi H. Chaouche M. Tazir M. Abbadi M.C. Immunoenzymatic determination of free immunoglobulin light chains in the cerebrospinal fluid: Its value in the biological diagnosis of multiple sclerosis Arch. L’institut Pasteur D’algerie. Inst. Pasteur D'algerie 1989 57 111 124 2518740
  88. [92]Diaz C.T.S. de Las Heras Flórez S. Perez M.C. Pérez M.Á.H. García V.M. Evaluation of Kappa Index as a Tool in the Diagnosis of Multiple Sclerosis: Implementation in Routine Screening Procedure Front. Neurol. 2021 12 676527 10.3389/fneur.2021.676527 34456842 PMC8386692 · DOI
  89. [93]Van der Heijden M. Kraneveld A. Redegeld F. Free immunoglobulin light chains as target in the treatment of chronic inflammatory diseases Eur. J. Pharmacol. 2006 533 319 326 10.1016/j.ejphar.2005.12.065 16455071 · DOI
  90. [94]Thio M. Blokhuis B.R. Nijkamp F.P. Redegeld F.A. Free immunoglobulin light chains: A novel target in the therapy of inflammatory diseases Trends Pharmacol. Sci. 2008 29 170 174 10.1016/j.tips.2008.01.004 18353446 · DOI
  91. [95]Sindic C.J. Laterre E.C. Oligoclonal free kappa and lambda bands in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. An immunoaffinity-mediated capillary blot study J. Neuroimmunol. 1991 33 63 72 10.1016/0165-5728(91)90035-6 1829093 · DOI
  92. [96]Fagnart O.C. Sindic C.J. Laterre C. Free kappa and lambda light chain levels in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases J. Neuroimmunol. 1988 19 119 132 10.1016/0165-5728(88)90041-0 3135296 · DOI
  93. [97]Ganelin-Cohen E. Golderman S. Yeskaraev R. Rozenberg A. Livneh A. Kaplan B. Search for new biomarkers of pediatric multiple sclerosis: Application of immunoglobulin free light chain analysis Clin. Chem. Lab. Med. 2018 56 1081 1089 10.1515/cclm-2017-0911 29408796 · DOI
  94. [98]Kaplan B. Golderman S. Yahalom G. Yeskaraev R. Ziv T. Aizenbud B.M. Sela B.-A. Livneh A. Free light chain monomer-dimer patterns in the diagnosis of multiple sclerosis J. Immunol. Methods 2013 390 74 80 10.1016/j.jim.2013.01.010 23376556 · DOI
  95. [99]Kaplan B. Aizenbud B.M. Golderman S. Yaskariev R. Sela B.A. Free light chain monomers in the diagnosis of multiple sclerosis J. Neuroimmunol. 2010 229 263 271 10.1016/j.jneuroim.2010.09.002 20870296 · DOI
  96. [100]Rinker J.R. 2nd Trinkaus K. Cross A.H. Elevated CSF free kappa light chains correlate with disability prognosis in multiple sclerosis Neurology 2006 67 1288 1290 10.1212/01.wnl.0000238107.31364.21 17030770 · DOI
  97. [101]Rudick R.A. Peter D.R. Bidlack J.M. Knutson D.W. Multiple sclerosis: Free light chains in cerebrospinal fluid Neurology 1985 35 1443 1449 10.1212/WNL.35.10.1443 3929159 · DOI
  98. [102]Rudick R.A. Pallant A. Bidlack J.M. Herndon R.M. Free kappa light chains in multiple sclerosis spinal fluid Ann. Neurol. 1986 20 63 69 10.1002/ana.410200111 3090930 · DOI
  99. [103]Vandvik B. Oligoclonal IgG and free light chains in the cerebrospinal fluid of patients with multiple sclerosis and infectious diseases of the central nervous system Scand. J. Immunol. 1977 6 913 922 10.1111/j.1365-3083.1977.tb00412.x 410092 · DOI
  100. [104]Eickhoff K. Heipertz R. Determination of immunoglobulin content of CSF based on light chain characteristics Ann. Neurol. 1978 3 509 512 10.1002/ana.410030610 98101 · DOI
  101. [105]Sidén A. Isoelectric focusing and crossed immunoelectrofocusing of CSF immunoglobulins in MS J. Neurol. 1979 221 39 51 10.1007/BF00313168 92535 · DOI
  102. [106]Link H. Laurenzi M.A. Immunoglobulin class and light chain type of oligoclonal bands in CSF in multiple sclerosis determined by agarose gel electrophoresis and immunofixation Ann. Neurol. 1979 6 107 110 10.1002/ana.410060205 115379 · DOI
  103. [107]Laurenzi M.A. Mavra M. Kam-Hansen S. Link H. Oligoclonal IgG and free chains in multiple sclerosis demonstrated by thin-layer polyacrylamide gel isoelectric focusing and immunofixation Ann. Neurol. 1980 8 241 247 10.1002/ana.410080304 6159820 · DOI
  104. [108]Rocchelli B. Poloni M. Mazzarello P. Delodovici M. Identification of the kappa and lambda light chains within the CSF immunoglobulin region in multiple sclerosis and subacute sclerosing panencephalitis by immunofixation after isoelectric focusing J. Neurol. 1981 226 169 179 10.1007/BF00313378 6172564 · DOI
  105. [109]Mattson D.H. Roos R.P. Hopper J.E. Arnason B.G. Light chain composition of CSF oligoclonal IgG bands in multiple sclerosis and subacute sclerosing panencephalitis J. Neuroimmunol. 1982 3 63 76 10.1016/0165-5728(82)90018-2 6808024 · DOI
  106. [110]Gallo P. Visentini E. Tavolato B. Study of the IgG oligoclonal bands in cerebral spinal fluid in multiple sclerosis by electroimmunofixation Ital. J. Neurol. Sci. 1982 3 311 315 10.1007/BF02043579 6820013 · DOI
  107. [111]Michałowska-Wender G. Losy J. Tokarz-Kupczyk E. Wygladalska-Jernas H. Wender M. Urine free light chains kappa in multiple sclerosis Neurol. Neurochir. Pol. 1999 33 311 319 10463246
  108. [112]Constantinescu C.S. Mehta P.D. Rostami A.M. Urinary free kappa light chain levels in chronic progressive multiple sclerosis Pathobiology 1994 62 29 33 10.1159/000163874 8031473 · DOI
  109. [113]Mehta P.D. Cook S.D. Troiano R.A. Coyle P.K. Increased free light chains in the urine from patients with multiple sclerosis Neurology 1991 41 540 544 10.1212/WNL.41.4.540 1901396 · DOI
  110. [114]Dobson R. Miller R.F. Palmer H.E. Feldmann M. Thompson E. Miller D. Giovannoni G. Thompson A. Increased urinary free immunoglobulin light chain excretion in patients with multiple sclerosis J. Neuroimmunol. 2010 220 99 103 10.1016/j.jneuroim.2010.01.012 20171744 · DOI
  111. [115]Totolian N.A. Griazeva I.V. Klimovich V.B. Totolian A.A. Free light-chain immunoglobulins in the biological fluids of patients with multiple sclerosis Zhurnal Nevrol. Psikhiatrii Im. SS Korsakova 1997 97 34 38 9245156
  112. [116]Kaplan B. Golderman S. Ganelin-Cohen E. Miniovitch A. Korf E. Ben-Zvi I. Livneh A. Flechter S. Immunoglobulin free light chains in saliva: A potential marker for disease activity in multiple sclerosis Clin. Exp. Immunol. 2018 192 7 17 10.1111/cei.13086 29194592 PMC5842412 · DOI
  113. [117]Lotan I. Ganelin-Cohen E. Tartakovsky E. Khasminsky V. Hellmann M.A. Steiner I. Ben-Zvi I. Livneh A. Golderman S. Kaplan B. Saliva immunoglobulin free light chain analysis for monitoring disease activity and response to treatment in multiple sclerosis Mult. Scler. Relat. Disord. 2020 44 102339 10.1016/j.msard.2020.102339 32599469 · DOI
  114. [118]Hannich M.J. Dressel A. Budde K. Petersmann A. Nauck M. Süße M. Kappa Free Light Chains in the Context of Blood Contamination, and Other IgA- and IgM-Related Cerebrospinal Fluid Disease Pattern Cells 2021 10 616 10.3390/cells10030616 33799494 PMC7998777 · DOI
  115. [119]Riddoch D. Thompson R.A. Immunoglobulin levels in the cerebrospinal fluid Br. Med. J. 1970 1 396 399 10.1136/bmj.1.5693.396 4190842 PMC1699195 · DOI
  116. [120]Schwenkenbecher P. Janssen T. Wurster U. Konen F.F. Neyazi A. Ahlbrecht J. Puppe W. Bönig L. Sühs K.-W. Stangel M. The Influence of Blood Contamination on Cerebrospinal Fluid Diagnostics Front. Neurol. 2019 10 584 10.3389/fneur.2019.00584 31249547 PMC6582628 · DOI
  117. [121]Cserti C. Haspel R. Stowell C. Dzik W. Light-chain removal by plasmapheresis in myeloma-associated renal failure Transfusion 2007 47 511 514 10.1111/j.1537-2995.2006.01143.x 17319833 · DOI
  118. [122]Fauci A.S. Mechanisms of corticosteroid action on lymphocyte subpopulations. I. Redistribution of circulating T and b lymphocytes to the bone marrow Immunology 1975 28 669 680 1080130 PMC1445841
  119. [123]Fauci A.S. Dale D.C. The effect of in vivo hydrocortisone on subpopulations of human lymphocytes J. Clin. Investig. 1974 53 240 246 10.1172/JCI107544 4808638 PMC301459 · DOI
  120. [124]Cohn L.A. The influence of corticosteroids on host defense mechanisms J. Vet. Intern. Med. 1991 5 95 104 10.1111/j.1939-1676.1991.tb00939.x 2061872 · DOI
  121. [125]Topping J. Dobson R. Lapin S. Maslyanskiy A. Kropshofer H. Leppert D. Giovannoni G. Evdoshenko E. The effects of intrathecal rituximab on biomarkers in multiple sclerosis Mult. Scler. Relat. Disord. 2016 6 49 53 10.1016/j.msard.2016.01.001 27063622 · DOI
  122. [126]Konen F.F. Schwenkenbecher P. Wurster U. Jendretzky K.F. Möhn N. Gingele S. Sühs K.W. Hannich M.J. Grothe M. Witte T. The influence of renal function impairment on kappa free light chains in cerebrospinal fluid J. Cent. Nerv. Syst. Dis. 2021 in press PMC8619759 34840504
  123. [127]Mooradian A.D. Effect of aging on the blood-brain barrier Neurobiol. Aging 1988 9 31 39 10.1016/S0197-4580(88)80013-7 3288893 · DOI
  124. [128]Jenner E. Serum free light chains in clinical laboratory diagnostics Clin. Chim. Acta 2014 427 15 20 10.1016/j.cca.2013.08.018 23999048 · DOI
  125. [129]Katzmann J.A. Clark R.J. Abraham R.S. Bryant S. Lymp J.F. Bradwell A.R. Kyle R.A. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains Clin. Chem. 2002 48 1437 1444 10.1093/clinchem/48.9.1437 12194920 · DOI
  126. [130]Makshakov G.S. Nazarov V.D. Totolyan N.A. Lapin S.V. Mazing A.V. Emanuel V.L. Krasnov V.S. Shumilina M.V. Skoromets A.A. Evdoshenko E.P. The association of intrathecal production of immunoglobulin free light chains and progression of multiple sclerosis Zhurnal Nevrol. Psikhiatrii Im. SS Korsakova 2017 117 4 10 10.17116/jnevro20171171024-10 29359727 · DOI
  127. [131]Reiber H. Peter J.B. Cerebrospinal fluid analysis: Disease-related data patterns and evaluation programs J. Neurol. Sci. 2001 184 101 122 10.1016/S0022-510X(00)00501-3 11239944 · DOI
  128. [132]Schwenkenbecher P. Wurster U. Konen F.F. Gingele S. Sühs K.-W. Wattjes M.P. Stangel M. Skripuletz T. Impact of the McDonald Criteria 2017 on Early Diagnosis of Relapsing-Remitting Multiple Sclerosis Front. Neurol. 2019 10 188 10.3389/fneur.2019.00188 30930829 PMC6428717 · DOI
  129. [133]Kuhle J. Disanto G. Dobson R. Adiutori R. Bianchi L. Topping J. Bestwick J.P. Meier U.-C. Marta M. Costa G.D. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study Mult. Scler. 2015 21 1013 1024 10.1177/1352458514568827 25680984 · DOI · Paper page
  130. [134]Franciotta D. Salvetti M. Lolli F. Serafini B. Aloisi F. B cells and multiple sclerosis Lancet Neurol. 2008 7 852 858 10.1016/S1474-4422(08)70192-3 18703007 · DOI
  131. [135]Nazarov V. Makshakov G. Kalinin I. Lapin S. Surkova E. Mikhailova L. Gilburd B. Skoromets A. Evdoshenko E. Concentrations of immunoglobulin free light chains in cerebrospinal fluid predict increased level of brain atrophy in multiple sclerosis Immunol. Res. 2018 66 761 767 10.1007/s12026-018-9058-8 30635824 · DOI
  132. [136]Gudowska-Sawczuk M. Czupryna P. Moniuszko-Malinowska A. Pancewicz S. Mroczko B. Free Immunoglobulin Light Chains in Patients with Tick-Borne Encephalitis: Before and after Treatment J. Clin. Med. 2021 10 2922 10.3390/jcm10132922 34209994 PMC8269011 · DOI
  133. [137]Tjernberg I. Johansson M. Henningsson A.J. Diagnostic performance of cerebrospinal fluid free light chains in Lyme neuroborreliosis—A pilot study Clin. Chem. Lab. Med. 2019 57 2008 2018 10.1515/cclm-2019-0315 31199760 · DOI
  134. [138]Hegen H. Milosavljevic D. Schnabl C. Manowiecka A. Walde J. Deisenhammer F. Presslauer S. Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis Clin. Chem. Lab. Med. 2018 56 1383 1391 10.1515/cclm-2018-0028 29648995 · DOI
  135. [139]Forsberg P. Frydén A. Link H. Immunoglobulin abnormalities in the cerebrospinal fluid during bacterial meningitis J. Neuroimmunol. 1986 12 299 310 10.1016/0165-5728(86)90036-6 3760156 · DOI
  136. [140]Sinclair A.J. Wienholt L. Tantsis E. Brilot F. Dale R.C. Clinical association of intrathecal and mirrored oligoclonal bands in paediatric neurology Dev. Med. Child Neurol. 2013 55 71 75 10.1111/j.1469-8749.2012.04443.x 23095051 · DOI
  137. [141]Vandvik B. Vartdal F. Norrby E. Herpes simplex virus encephalitis: Intrathecal synthesis of oligoclonal virus-specific IgG, IgA and IgM antibodies J. Neurol. 1982 228 25 38 10.1007/BF00313407 6184456 · DOI

Authors
Konen, F. F., Schwenkenbecher, P., Jendretzky, K. F., Gingele, S., Sühs, K.-W., Tumani, H., Süße, M., & Skripuletz, T.
Affiliations
  • Medizinische Hochschule Hannover (DE)
  • Universität Ulm (DE)
  • Universitätsmedizin Greifswald (DE)
Corresponding author
Skripuletz, Thomas
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-11-06
Volume
10
Issue
11
Pages
3056
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells10113056
PMC
PMC8622045
OpenAlex
W3214224030
Cited by
47
References
142
Citations by year
2026: 12 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 12
FWCI
1.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • OPen Access Repositorium der Universität Ulm (OPARU) (Ulm University) (submittedVersion, cc-by)
  • Universität Ulm, Kommunikations- und Informationszentrum (kiz) (cc-by)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords
kappa free light chains, multiple sclerosis, intrathecal inflammation, biomarkers, oligoclonal bands, blood-CSF barrier, albumin quotient, diagnostic thresholds, neuroinflammatory diseases, antibody production
MeSH terms
Animals, Brain, Humans, Immunoglobulin kappa-Chains, Immunoglobulin Light Chains, Multiple Sclerosis, Biomarkers, Disease Progression

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