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

Manfred Uhr, Marie Süße, Malte Hannich, Manfred Wick, Herwig Strik, Annette Spreer, Martin Roskos, Stefan Isenmann, Andrea Harrer, Peter Eichhorn, Catharina C Groß, Andreas Gerritzen, Ulrich Wurster, Franz F Konen, Philipp Schwenkenbecher, Frank Leypoldt, Hayrettin Tumani, Markus Otto, Jan Lewerenz, Thomas Zimmermann, Jens Wiltfang, Piotr Lewczuk, Klemens Ruprecht, Brigitte Wildemann, Michael Khalil, Axel Regeniter, Thomas Skripuletz

Journal: Autoimmunity reviews 2025;24(5):103765

PMID: 39947571

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.

Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.

Address: Department of Neurology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: [email protected].; Department of Neurology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: [email protected].; Department of Neurology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: [email protected].; Medical Laboratory Bremen, 28357 Bremen, Germany. Electronic address: [email protected].; Department of Neurology with Institute of Translational Neurology, University Hospital and University Münster, 48149 Münster, Germany. Electronic address: [email protected].; Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 81377 München, Germany. Electronic address: [email protected].; Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Centre for Cognitive Neuroscience, 5020 Salzburg, Austria; Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria. Electronic address: [email protected].; Department of Neurology, GFO Kliniken Niederrhein, St. Josef Krankenhaus Moers, 47441 Moers, Germany. Electronic address: [email protected].; Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Department of Neurodegeneration Diagnostics, Medical University of Białystok, and Department of Biochemical Diagnostics, University Hospital of Białystok, 15-269 Białystok, Poland. Electronic address: [email protected].; Department of Neurology, University of Ulm, 89081 Ulm, Germany. Electronic address: [email protected].; Institute of Clinical Chemistry and Department of Neurology, University Hospital Schleswig-Holstein and Kiel University, 24105 Kiel, Germany. Electronic address: [email protected].; Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) 06120, Germany. Electronic address: [email protected].; Infectious Disease Serology and Immunology, Medica Medizinische Laboratorien Dr. F. Kaeppeli AG, 8032 Zurich, Switzerland. Electronic address: [email protected].; SYNLAB Holding Deutschland GmbH, 86156 Augsburg, Germany. Electronic address: [email protected].; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany. Electronic address: [email protected].; Department of Neurology, Klinikum Braunschweig, 38126 Braunschweig, Germany. Electronic address: [email protected].; Department of Neurology, Sozialstiftung Bamberg, 96049 Bamberg, Germany. Electronic address: [email protected].; Department of Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany. Electronic address: [email protected].; Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 81377 München, Germany. Electronic address: [email protected].; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, 69120 Heidelberg, Germany. Electronic address: [email protected].; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, 37075 Göttingen, Germany. Electronic address: [email protected].; Labopart Medical Laboratories, 01127 Dresden, Germany. Electronic address: [email protected].; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17489 Greifswald, Germany. Electronic address: [email protected].; Department of Neurology, Medical University of Graz, 8036 Graz, Austria. Electronic address: [email protected].; Department of Neurology, University of Ulm, 89081 Ulm, Germany. Electronic address: [email protected].; Department of Neurology, University Medicine Greifswald, Germany. Electronic address: [email protected].; Department of Neurology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: [email protected].
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