Beyond oligoclonal bands: the independent role of kappa free light chains in the diagnostic workup of multiple sclerosis

Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G et al (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17(2):162–173. https://doi.org/10.1016/s1474-4422(17)30470-2. (Epub 20171221)

Article  PubMed  Google Scholar 

Compston A, Coles A (2008) Multiple sclerosis. Lancet 372(9648):1502–1517. https://doi.org/10.1016/s0140-6736(08)61620-7. (PubMed PMID: 18970977.)

Article  CAS  PubMed  Google Scholar 

Gastaldi M, Zardini E, Franciotta D (2017) An update on the use of cerebrospinal fluid analysis as a diagnostic tool in multiple sclerosis. Expert Rev Mol Diagn 17(1):31–46. https://doi.org/10.1080/14737159.2017.1262260. (Epub 20161202)

Article  CAS  PubMed  Google Scholar 

Andersson M, Alvarez-Cermeño J, Bernardi G, Cogato I, Fredman P, Frederiksen J et al (1994) Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 57(8):897–902. https://doi.org/10.1136/jnnp.57.8.897. (PubMed PMID: 8057110; PubMed Central PMCID: PMC1073070.)

Article  CAS  PubMed  PubMed Central  Google Scholar 

Uccelli A, Aloisi F, Pistoia V (2005) Unveiling the enigma of the CNS as a B-cell fostering environment. Trends Immunol 26(5):254–259. https://doi.org/10.1016/j.it.2005.02.009. (PubMed PMID: 15866238.)

Article  CAS  PubMed  Google Scholar 

Montalban X, Lebrun-Frénay C, Oh J, Arrambide G, Moccia M, Pia Amato M et al (2025) Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol 24(10):850–865. https://doi.org/10.1016/s1474-4422(25)00270-4. (PubMed PMID: 40975101.)

Article  PubMed  Google Scholar 

Lamers KJ, de Jong JG, Jongen PJ, Kock-Jansen MJ, Teunesen MA, Prudon-Rosmulder EM (1995) Cerebrospinal fluid free kappa light chains versus IgG findings in neurological disorders: qualitative and quantitative measurements. J Neuroimmunol 62(1):19–25. https://doi.org/10.1016/0165-5728(95)00086-h. (PubMed PMID: 7499488.)

Article  CAS  PubMed  Google Scholar 

Nakano T, Matsui M, Inoue I, Awata T, Katayama S, Murakoshi T (2011) Free immunoglobulin light chain: its biology and implications in diseases. Clin Chim Acta 412(11–12):843–849. https://doi.org/10.1016/j.cca.2011.03.007. (Epub 20110315)

Article  CAS  PubMed  Google Scholar 

Hegen H, Walde J, Berek K, Arrambide G, Gnanapavan S, Kaplan B et al (2023) Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: a systematic review and meta-analysis. Mult Scler 29(2):169–181. https://doi.org/10.1177/13524585221134213. (Epub 20221201)

Article  CAS  PubMed  Google Scholar 

Ferraro D, Bedin R, Natali P, Franciotta D, Smolik K, Santangelo M et al (2020) Kappa index versus CSF oligoclonal bands in predicting multiple sclerosis and infectious/inflammatory CNS disorders. Diagnostics (Basel). https://doi.org/10.3390/diagnostics10100856

Article  PubMed  PubMed Central  Google Scholar 

Maglio G, D’Agostino M, Caronte FP, Pezone L, Casamassimi A, Rienzo M et al (2024) Multiple sclerosis: from the application of oligoclonal bands to novel potential biomarkers. Int J Mol Sci. https://doi.org/10.3390/ijms25105412. (Epub 20240515)

Article  PubMed  PubMed Central  Google Scholar 

Schwenkenbecher P, Konen FF, Wurster U, Witte T, Gingele S, Sühs KW et al (2019) Reiber’s diagram for kappa free light chains: the new standard for assessing intrathecal synthesis? Diagnostics. https://doi.org/10.3390/diagnostics9040194. (Epub 20191116)

Article  PubMed  PubMed Central  Google Scholar 

Hegen H, Schmidauer M, Auer M, Di Pauli F, Berek K, Walde J et al (2025) Kappa Free Light Chain Index in the real world-do we miss clinically relevant information by skipping oligoclonal banding? Eur J Neurol 32(9):e70355. https://doi.org/10.1111/ene.70355. (PubMed PMID: 40913362; PubMed Central PMCID: PMC12413532.)

Article  PubMed  PubMed Central  Google Scholar 

Villar LM, Masjuan J, Sádaba MC, González-Porqué P, Plaza J, Bootello A et al (2005) Early differential diagnosis of multiple sclerosis using a new oligoclonal band test. Arch Neurol 62(4):574–577. https://doi.org/10.1001/archneur.62.4.574. (PubMed PMID: 15824255.)

Article  PubMed  Google Scholar 

Teunissen C, Menge T, Altintas A, Álvarez-Cermeño JC, Bertolotto A, Berven FS et al (2013) Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis. Mult Scler 19(13):1802–1809. https://doi.org/10.1177/1352458513488232. (Epub 20130521)

Article  PubMed  Google Scholar 

Candeloro R, Galloppa M, Lombardo L, Laudisi M, Ghisellini S, Negri G et al (2024) Kappa free light chains in multiple sclerosis as a marker of intrathecal humoral response: a sex-disaggregated study. Diagnostics 14(24):2798. https://doi.org/10.3390/diagnostics14242798

Article  CAS  PubMed  PubMed Central  Google Scholar 

Castellazzi M, Morotti A, Tamborino C, Alessi F, Pilotto S, Baldi E et al (2020) Increased age and male sex are independently associated with higher frequency of blood-cerebrospinal fluid barrier dysfunction using the albumin quotient. Fluids Barriers CNS 17(1):14. https://doi.org/10.1186/s12987-020-0173-2. (Epub 20200205)

Article  CAS  PubMed  PubMed Central  Google Scholar 

Reiber H (1994) Flow rate of cerebrospinal fluid (CSF)--a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 122(2):189–203. https://doi.org/10.1016/0022-510x(94)90298-4. (PubMed PMID: 8021703.)

Article  CAS  PubMed  Google Scholar 

Candeloro R, Ferri C, Bellini T, Pugliatti M, Castellazzi M (2024) Breaking barriers: unveiling sex-related differences in cerebrospinal fluid analysis-a narrative review. Biology (Basel). https://doi.org/10.3390/biology13060420. (Epub 20240605)

Article  PubMed  PubMed Central  Google Scholar 

Vecchio D, Puricelli C, Virgilio E, Passarelli F, Guida S, Naldi P et al (2024) Kappa index for multiple sclerosis diagnosis: an accurate biomarker of intrathecal synthesis. J Neurol 272(1):30. https://doi.org/10.1007/s00415-024-12826-y. (Epub 20241212)

Article  CAS  PubMed  Google Scholar 

Sindic CJ, Laterre EC (1991) 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 33(1):63–72. https://doi.org/10.1016/0165-5728(91)90035-6. (PubMed PMID: 1829093)

Article  CAS  PubMed  Google Scholar 

Konen FF, Wurster U, Witte T, Jendretzky KF, Gingele S, Tumani H et al (2020) The impact of immunomodulatory treatment on kappa free light chains as biomarker in neuroinflammation. Cells. https://doi.org/10.3390/cells9040842. (Epub 20200331)

Article  PubMed  PubMed Central  Google Scholar 

Duell F, Högelin KA, Vlad B, Neidhart S, Khademi M, Jelcic I et al (2025) Kappa Free Light Chain Index correlates with prognostic biomarkers in multiple sclerosis and decreases slowly following treatment. Eur J Neurol 32(7):e70291. https://doi.org/10.1111/ene.70291. (PubMed PMID: 40643211; PubMed Central PMCID: PMC12247182.)

Article  PubMed  PubMed Central  Google Scholar 

Franciotta D, Salvetti M, Lolli F, Serafini B, Aloisi F (2008) B cells and multiple sclerosis. Lancet Neurol 7(9):852–858. https://doi.org/10.1016/s1474-4422(08)70192-3. (PubMed PMID: 18703007.)

Article  CAS  PubMed  Google Scholar 

Petzold A (2013) Intrathecal oligoclonal IgG synthesis in multiple sclerosis. J Neuroimmunol 262(1–2):1–10. https://doi.org/10.1016/j.jneuroim.2013.06.014. (Epub 20130726)

Article  CAS  PubMed  Google Scholar 

Comments (0)

No login
gif