ORIGINAL RESEARCH article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Kappa Free Light Chain index in CSF diagnostics: The impact of different Immunoglobulin Isotypes
Provisionally accepted
Martin Schmidauer1
Klaus Berek1
Michael Auer1
Franziska Di Pauli1
Fabian Föttinger2
Nik Krajnc2
Florian Deisenhammer1
Gabriel Bsteh2
Janette Walde3
Harald Hegen1*- 1Innsbruck Medical University, Innsbruck, Austria
- 2Medizinische Universitat Wien, Vienna, Austria
- 3Universitat Innsbruck Fakultat fur Volkswirtschaft und Statistik, Innsbruck, Austria
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Background: The kappa free light chain (k-FLC) index is a sensitive marker of intrathecal immunoglobulin (Ig) synthesis and is increasingly used in cerebrospinal fluid (CSF) analysis of patients with suspected multiple sclerosis (MS). The relative contribution of the diferent Ig isotypes to intrathecal k-FLC production remains unclear. Methods: We retrospectively analysed CSF data from patients with a first demyelinating event suggestive of MS enrolled in studies at the Medical Universities of Innsbruck and Vienna. Of all included patients, results on Ig and k-FLC concentrations in CSF and serum were available. Linear regression analysis was used to assess the impact of Ig intrathecal fractions (IF) on k-FLC index. Results: A total of 188 patients with a median age of 31 (25-39) years and a predominantly female sex distribution (62%) were included. The k-FLC index was significantly higher in patients with isolated intrathecal IgG synthesis [32.5 (17.7-81.0); n=130] compared to patients without intrathecal immunoglobulin production [3.0 (2.0-5.9); p<0.001; n=18] and was further elevated in patients with both intrathecal IgG and IgM synthesis [68.4 (48.4-120.6); n=29]. Both IgG and IgM IF independently contributed to the k-FLC index in linear regression analysis, with IgG IF having approximately 3.5 times the efect size of IgM IF. Exploratory analysis of the contribution of IgA IF to k-FLC index revealed qualitatively the same results. Conclusion: Increase of k-FLC index in patients with MS is predominantly due to an intrathecal IgG synthesis, while the contribution of intrathecal IgM is less frequent and quantitatively low.
Keywords: biomarker, Crebrospinal fluid, diagnostic, IgG, IgM, Kappa (κ) FLC, Multiple Sclerosis
Received: 16 Nov 2025; Accepted: 31 Jan 2026.
Copyright: © 2026 Schmidauer, Berek, Auer, Di Pauli, Föttinger, Krajnc, Deisenhammer, Bsteh, Walde and Hegen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Harald Hegen
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