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Review
. 2025 Apr 30;24(5):103765.
doi: 10.1016/j.autrev.2025.103765. Epub 2025 Feb 11.

Oligoclonal bands and kappa free light chains: Competing parameters or complementary biomarkers?

Franz F Konen  1 , Ulrich Wurster  2 , Philipp Schwenkenbecher  3 , Andreas Gerritzen  4 , Catharina C Groß  5 , Peter Eichhorn  6 , Andrea Harrer  7 , Stefan Isenmann  8 , Piotr Lewczuk  9 , Jan Lewerenz  10 , Frank Leypoldt  11 , Markus Otto  12 , Axel Regeniter  13 , Martin Roskos  14 , Klemens Ruprecht  15 , Annette Spreer  16 , Herwig Strik  17 , Manfred Uhr  18 , Manfred Wick  19 , Brigitte Wildemann  20 , Jens Wiltfang  21 , Thomas Zimmermann  22 , Malte Hannich  23 , Michael Khalil  24 , Hayrettin Tumani  25 , Marie Süße  26 , Thomas Skripuletz  27 ; German Society for Cerebrospinal Fluid Diagnostics and Clinical Neurochemistry (DGLN e.V.)
Affiliations
Free article
Review

Oligoclonal bands and kappa free light chains: Competing parameters or complementary biomarkers?

Franz F Konen et al. Autoimmun Rev. .
Free article

Abstract

Background: The 2024-revised McDonald criteria for multiple sclerosis (MS) proposed to incorporate cerebrospinal fluid (CSF)-specific oligoclonal bands and kappa free light chains (KFLC) as diagnostic biomarkers. While the 2017-revised criteria highlighted CSF-specific oligoclonal bands to indicate intrathecal IgG synthesis, significantly enhancing early MS diagnosis, KFLC have emerged as additional marker. Now, the question rises of whether both biomarkers serve as competing or complementary tools in MS diagnostics.

Methods: In this narrative review, we extensively searched the literature on oligoclonal bands and KFLC determination in CSF and serum across neurological disorders, with a focus on MS, using the PubMed database to demonstrate the complementarity of both biomarkers.

Results: Oligoclonal bands have long been a reliable marker of intrathecal IgG synthesis in MS, valued for their high diagnostic sensitivity, unique patient "fingerprints," clonality differentiation, semi-quantitative analysis, and pre-analytic robustness. However, they present challenges in standardization, labor-intensity, method variability, examiner dependency, and limited data on non-IgG immunoglobulins. Quantitative KFLC measurement provides rapid, examiner-independent, and cost-effective assessment across all immunoglobulin classes but might have lower specificity, lacked consensus on standardized interpretation in recent years, and is not yet supported by comprehensive prospective multinational studies on its prognostic role.

Conclusion: Both oligoclonal bands and KFLC have unique strengths and limitations that complement each other, potentially serving as complementary markers for evaluating intrathecal Ig synthesis in MS diagnosis. Further evidence is needed to establish the value of KFLC in MS diagnosis, thus multicenter prospective studies are being conducted to compare the diagnostic utility of both markers.

Keywords: Biomarker; Cerebrospinal fluid; Kappa free light chains; McDonald criteria; Multiple sclerosis; Oligoclonal bands; Reiber's diagram.

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Conflict of interest statement

Declaration of competing interest The authors report no competing interests. Outside the submitted work the author report the following. Franz Felix Konen received compensation for travelling and lectures from Merck, Novartis, BMS and Alexion as well as a Hannover Medical School (MHH)- and German Research Foundation (DFG)–funded fellowship as part of the Clinician Scientist Program (PRACTIS) at MHH. Ulrich Wurster has no conflicts to declare. Philipp Schwenkenbecher has no conflicts to declare. Andreas Gerritzen has no conflicts to declare. Catharina C. Gross received speaker honoraria from MyLan and DIU Dresden International University GmbH, and travel expenses for attending meetings from Biogen, Euroimmun, MyLan, and Novartis Pharma. Her research is funded by the German Research Foundation (DFG), the European Union (Horizon2020), the IZKF Münster, Biogen, Roche, and Novartis. Peter Eichhorn has no conflicts to declare. Andrea Harrer has no conflicts to declare. Stefan Isenmann has no conflicts to declare. Piotr Lewczuk has no conflicts to declare. Jan Lewerenz reports travel honoraria and speakers fees from the Cure Huntington's Disease Initiative CHDI, the Movement Disorders Society as the German Society for Cerebrospinal Fluid Diagnostic and Clinical Neurochemistry DGLN. His institution received financial compensation for clinical trials with JL as principal investigator from CHDI. He is member of the executive board of the DGLN. He received research funding from the German Federal Ministry of Education and Research BMBF. Frank Leypoldt reports not conflicts regarding the present work. Independent of this work, FL is supported by the German Federal Ministry of Education and Research (CONNECT-GENERATE grant no. 01GM1908A and 01GM2208), E-Rare Joint Transnational research support (ERA-Net, LE3064/2–1), Stiftung Pathobiochemie of the German Society for Laboratory Medicine and HORIZON MSCA 2022 Doctoral Network 101,119,457 — IgG4-TREAT and discloses speaker honoraria from Grifols, Teva, Biogen, Bayer, Roche, Novartis, Fresenius, travel funding from Merck, Grifols and Bayer and serving on advisory boards for Roche, Biogen and Alexion. Markus Otto has no conflicts to declare concerning this manuscript. Independent from this work MO received research support from the EU Joint Programme-Neurodegenerative Diseases networks Genfi-Prox, the EU (MOODMARKER), the German Research Foundation/DFG (SFB1279), the foundation of the state Baden-Württemberg (D.3830), Boehringer Ingelheim Ulm University BioCenter (D.5009), and the Thierry Latran Foundation. MO obtained served as scientific advisor for Fujirebio, Biogen, Axon, Lilly. Axel Regeniter has no conflicts to declare concerning this manuscript. Martin Roskos has no conflicts to declare. Klemens Ruprecht received research support from Novartis, Merck Serono, German Ministry of Education and Research, European Union (821283–2), Stiftung Charité, Guthy-Jackson Charitable Foundation, and Arthur Arnstein Foundation; received speaker's honoraria from Virion Serion and Novartis. Annette Spreer has no conflicts to declare. Herwig Strik reports personal fees from Alexion, Biogen, Daichii-Sankyo, Bayer and CSL Behring. Manfred Uhr has no conflicts to declare. Manfred Wick has no conflicts to declare. Brigitte Wildemann reports grants from the German Ministry of Education and Research, Deutsche Forschungsgemeinschaft, Dietmar Hopp Foundation, Klaus Tschira Foundation, grants and personal fees from Merck, Novartis, Roche, and personal fees from Alexion, INSTAND, Roche. Jens Wiltfang has no conflicts to declare. Thomas Zimmermann has no conflicts to declare. Malte Hannich has no conflicts to declare. Hayrettin Tumani reports funding for research projects, lectures, and travel from Alexion, Bayer, Biogen, Celgene, Genzyme-Sanofi, Merck, Novartis, Roche, Teva, and received acknowledges research support from DMSG, MWK-BW, University of Ulm, and BMBF and Chemische Fabrik Karl Bucher. Michael Khalil has received travel funding and speaker honoraria from Bayer, Biogen, Novartis, Merck, Sanofi and Teva and serves on scientific advisory boards for Biogen, Bristol-Myers Squibb, Gilead, Merck, Novartis, Alexion and Roche. He received research grants from Biogen, Novartis and Teva. Marie Süße has no conflicts to declare. Thomas Skripuletz reports research support from Alnylam Pharmaceuticals, CSL Behring, Novartis, Siemens; honoraria for lectures and travel expenses for attending meetings from Alexion, Alnylam Pharmaceuticals, argenx, Bayer Vital, Biogen, Bristol Myers Squibb, Celgene, Centogene, CSL Behring, Euroimmun, Grifols, Hexal AG, Horizon, Janssen-Cilag, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Swedish Orphan Biovitrum, Teva, Viatris; consultant fees from Alexion, Alnylam Pharmaceuticals, Biogen, Centogene, CSL Behring, Grifols, Hexal AG, Janssen-Cilag, Merck Serono, Novartis, Roche, Sanofi, Swedish Orphan Biovitrum, Viatris.

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