Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal

Silvia Graciela Ramos; Andrés Maria Villa; Analisa Manin; Viviana Novoa; Claudio Aranda

doi:doi:10.11648/j.iji.20251304.12

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Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal

Silvia Graciela Ramos^*, Andrés Maria Villa, Analisa Manin, Viviana Novoa, Claudio Aranda

Published in International Journal of Immunology (Volume 13, Issue 4)

Received: 24 November 2025 Accepted: 6 December 2025 Published: 29 December 2025

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Abstract

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) analysis, including oligoclonal bands (OCB) and the IgG index, is central to MS diagnosis but presents technical and interpretative limitations. The kappa free light chain (κFLC) index has emerged as a promising biomarker of intrathecal immunoglobulin synthesis. Objective: To evaluate the diagnostic performance of the κFLC index in MS, determine an optimal cutoff value, and compare its accuracy with OCB detection and the IgG index. Methods: We conducted a retrospective study including 176 patients evaluated at the Neuroimmunology Laboratory of Buenos Aires, Argentina. Patients were classified into four groups: MS (n = 106), neuromyelitis optica spectrum disorders (NMOSD, n = 15), other inflammatory CNS disorders of autoimmune or infectious origin (ICNSDAI, n = 41), and paraneoplastic neurological syndromes (PNS, n = 14). κFLC, IgG, and albumin concentrations were measured in paired CSF and serum samples. The κFLC index was calculated and compared with OCB and IgG index results. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: The κFLC index was significantly higher in MS patients (median: 85; IQR: 30–305) compared with NMOSD (3.37), ICNSDAI (1.62), and PNS (1.96) groups (p < 0.0001). A κFLC index cutoff of 15 demonstrated 92% sensitivity and 83% specificity, with an area under the ROC curve of 0.952. The κFLC index correlated with the IgG index (ρ = 0.587, p < 0.0001) and OCB positivity (ρ = 0.586, p < 0.0001). κFLC index values ≥100 were observed almost exclusively in MS, with one exception in a patient with acute HSV-1 encephalitis. Conclusion: The κFLC index is a sensitive and reliable biomarker for intrathecal immunoglobulin synthesis in MS, offering advantages of automation, rapid processing, and objective quantification. External validation in independent cohorts is required before routine clinical implementation.

Published in	International Journal of Immunology (Volume 13, Issue 4)
DOI	10.11648/j.iji.20251304.12
Page(s)	90-95
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Multiple Sclerosis, Cerebrospinal Fluid, Kappa Free Light Chains, Oligoclonal Bands, Intrathecal Immunoglobulin Synthesis, Biomarkers

References

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[2]	Smith Simonsen C, Flemmen HØ, Lauritzen T, Berg-Hansen P, Moen SM, et al. (2020) The diagnostic value of IgG index versus oligoclonal bands in cerebrospinal fluid of patients with multiple sclerosis. Multiple Sclerosis Journal – Experimental, Translational and Clinical Volume 6, Issue 1, January 2020 https://doi.org/10.1177/2055217319901291
[3]	Kaplan B, Aizenbud BM, Golderman S, Yaskariev R, Sela BA. (2010) Free light chain monomers in the diagnosis of multiple sclerosis. J Neuroimmunol. Dec 15; 229(1-2): 263-71. https://doi.org/10.1016/j.jneuroim.2010.09.002
[4]	Presslauer S, Milosavljevic D, Brücke T, Bayer P, Hübl W, et al. (2008) Elevated levels of kappa free light chains in CSF support the diagnosis of multiple sclerosis. J. Neurol. 255, 1508–14. https://doi.org/10.1007/s00415-008-0954-z
[5]	Nakano T, Matsui M, Inoue I, et al. (2011) Free immunoglobulin light chain: Its biology and implications in diseases. Clin Chim Acta 2011; 412: 843–849.
[6]	Hassan-Smith G, Durant L, Tsentemeidou A, Assi LK, Faint JM, et al. (2014) High sensitivity and specificity of elevated cerebrospinal fluid kappa free light chains in suspected multiple sclerosis. J Neuroimmunol. 2014 Nov 15; 276(1-2): 175-9. https://doi.org/10.1016/j.jneuroim.2014.08.003
[7]	Dekeyser C, De Kesel P, Cambron M, Vanopdenbosch L, Van Hijfte L, et al. (2024) Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis. Front. Immunol., 29 April 2024. Sec. Multiple Sclerosis and Neuroimmunology. Volume 15 - 2024 \| https://doi.org/10.3389/fimmu.2024.1385231
[8]	Sarthou A, Chrétien P, Giorgi L, Chiron A, Leroy C, et al. (2024) The kappa free light chains index is an accurate diagnostic biomarker for paediatric multiple sclerosis. Mult Scler. 2024 Oct; 30(11-12): 1436-1444. https://doi.org/10.1177/13524585241274034
[9]	Moreno?Navarro L, Mora?Diaz S, Ruiz?Escribano?Menchen L, Sempere A. (2025) Kappa free light chain index as a diagnostic and prognostic biomarker in multiple sclerosis. Journal of Neurology 272: 646. https://doi.org/10.1007/s00415-025-13381-w
[10]	Abid MA, Ahmed S, Muneer S, Khan S, de Oliveira MHS, Kausar R et al (2023) Evaluation of CSF kappa free light chains for the diagnosis of multiple sclerosis (MS): a comparison with oligoclonal bands (OCB) detection via isoelectric focusing (IEF) coupled with immunoblotting. J Clin Pathol 76(5): 353–356. https://doi.org/10.1136/jcp-2022-208354
[11]	Morello M, Mastrogiovanni S, Falcione F, Rossi V, Bernardini S, Casciani S et al (2024) Laboratory diagnosis of intrathecal synthesis of immunoglobulins: a review about the contribution of OCBs and K-index. Int J Mol Sci 25(10): 5170. https://doi.org/10.3390/ijms25105170
[12]	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
[13]	Monreal E, Fernández-Velasco JI, García-Soidán A, Sainz de la Maza S, Espiño M, Villarrubia N et al (2023) Establishing the best combination of the kappa free light chain index and oligoclonal bands for an accurate diagnosis of multiple sclerosis. Front Immunol 14: 1288169. https://doi.org/10.3389/fimmu.2023.1288169
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APA Style

Ramos, S. G., Villa, A. M., Manin, A., Novoa, V., Aranda, C. (2025). Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal. International Journal of Immunology, 13(4), 90-95. https://doi.org/10.11648/j.iji.20251304.12

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ACS Style

Ramos, S. G.; Villa, A. M.; Manin, A.; Novoa, V.; Aranda, C. Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal. Int. J. Immunol. 2025, 13(4), 90-95. doi: 10.11648/j.iji.20251304.12

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AMA Style

Ramos SG, Villa AM, Manin A, Novoa V, Aranda C. Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal. Int J Immunol. 2025;13(4):90-95. doi: 10.11648/j.iji.20251304.12

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@article{10.11648/j.iji.20251304.12,
  author = {Silvia Graciela Ramos and Andrés Maria Villa and Analisa Manin and Viviana Novoa and Claudio Aranda},
  title = {Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal},
  journal = {International Journal of Immunology},
  volume = {13},
  number = {4},
  pages = {90-95},
  doi = {10.11648/j.iji.20251304.12},
  url = {https://doi.org/10.11648/j.iji.20251304.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20251304.12},
  abstract = {Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) analysis, including oligoclonal bands (OCB) and the IgG index, is central to MS diagnosis but presents technical and interpretative limitations. The kappa free light chain (κFLC) index has emerged as a promising biomarker of intrathecal immunoglobulin synthesis. Objective: To evaluate the diagnostic performance of the κFLC index in MS, determine an optimal cutoff value, and compare its accuracy with OCB detection and the IgG index. Methods: We conducted a retrospective study including 176 patients evaluated at the Neuroimmunology Laboratory of Buenos Aires, Argentina. Patients were classified into four groups: MS (n = 106), neuromyelitis optica spectrum disorders (NMOSD, n = 15), other inflammatory CNS disorders of autoimmune or infectious origin (ICNSDAI, n = 41), and paraneoplastic neurological syndromes (PNS, n = 14). κFLC, IgG, and albumin concentrations were measured in paired CSF and serum samples. The κFLC index was calculated and compared with OCB and IgG index results. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: The κFLC index was significantly higher in MS patients (median: 85; IQR: 30–305) compared with NMOSD (3.37), ICNSDAI (1.62), and PNS (1.96) groups (p < 0.0001). A κFLC index cutoff of 15 demonstrated 92% sensitivity and 83% specificity, with an area under the ROC curve of 0.952. The κFLC index correlated with the IgG index (ρ = 0.587, p < 0.0001) and OCB positivity (ρ = 0.586, p < 0.0001). κFLC index values ≥100 were observed almost exclusively in MS, with one exception in a patient with acute HSV-1 encephalitis. Conclusion: The κFLC index is a sensitive and reliable biomarker for intrathecal immunoglobulin synthesis in MS, offering advantages of automation, rapid processing, and objective quantification. External validation in independent cohorts is required before routine clinical implementation.},
 year = {2025}
}

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TY  - JOUR
T1  - Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal
AU  - Silvia Graciela Ramos
AU  - Andrés Maria Villa
AU  - Analisa Manin
AU  - Viviana Novoa
AU  - Claudio Aranda
Y1  - 2025/12/29
PY  - 2025
N1  - https://doi.org/10.11648/j.iji.20251304.12
DO  - 10.11648/j.iji.20251304.12
T2  - International Journal of Immunology
JF  - International Journal of Immunology
JO  - International Journal of Immunology
SP  - 90
EP  - 95
PB  - Science Publishing Group
SN  - 2329-1753
UR  - https://doi.org/10.11648/j.iji.20251304.12
AB  - Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) analysis, including oligoclonal bands (OCB) and the IgG index, is central to MS diagnosis but presents technical and interpretative limitations. The kappa free light chain (κFLC) index has emerged as a promising biomarker of intrathecal immunoglobulin synthesis. Objective: To evaluate the diagnostic performance of the κFLC index in MS, determine an optimal cutoff value, and compare its accuracy with OCB detection and the IgG index. Methods: We conducted a retrospective study including 176 patients evaluated at the Neuroimmunology Laboratory of Buenos Aires, Argentina. Patients were classified into four groups: MS (n = 106), neuromyelitis optica spectrum disorders (NMOSD, n = 15), other inflammatory CNS disorders of autoimmune or infectious origin (ICNSDAI, n = 41), and paraneoplastic neurological syndromes (PNS, n = 14). κFLC, IgG, and albumin concentrations were measured in paired CSF and serum samples. The κFLC index was calculated and compared with OCB and IgG index results. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: The κFLC index was significantly higher in MS patients (median: 85; IQR: 30–305) compared with NMOSD (3.37), ICNSDAI (1.62), and PNS (1.96) groups (p < 0.0001). A κFLC index cutoff of 15 demonstrated 92% sensitivity and 83% specificity, with an area under the ROC curve of 0.952. The κFLC index correlated with the IgG index (ρ = 0.587, p < 0.0001) and OCB positivity (ρ = 0.586, p < 0.0001). κFLC index values ≥100 were observed almost exclusively in MS, with one exception in a patient with acute HSV-1 encephalitis. Conclusion: The κFLC index is a sensitive and reliable biomarker for intrathecal immunoglobulin synthesis in MS, offering advantages of automation, rapid processing, and objective quantification. External validation in independent cohorts is required before routine clinical implementation.
VL  - 13
IS  - 4
ER  -

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Author Information

Silvia Graciela Ramos

Immunology Laboratory, General Acute Care Hospital Dr. Carlos G. Durand, Buenos Aires, Argentina

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Andrés Maria Villa

Neurology Division. General Acute Care Hospital Dr. José María Ramos Mejía, Buenos Aires, Argentina;Argentine Center for Neuroimmunology (CADENI), University of Buenos Aires, Buenos Aires, Argentina

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Analisa Manin

Neurology Division. General Acute Care Hospital Dr. José María Ramos Mejía, Buenos Aires, Argentina;Argentine Center for Neuroimmunology (CADENI), University of Buenos Aires, Buenos Aires, Argentina

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Viviana Novoa

Immunology Laboratory, General Acute Care Hospital Dr. Carlos G. Durand, Buenos Aires, Argentina

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Claudio Aranda

Central Laboratory Division, General Acute Care Hospital Dr. Carlos G. Durand, Buenos Aires, Argentina

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APA Style

Ramos, S. G., Villa, A. M., Manin, A., Novoa, V., Aranda, C. (2025). Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal. International Journal of Immunology, 13(4), 90-95. https://doi.org/10.11648/j.iji.20251304.12

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ACS Style

Ramos, S. G.; Villa, A. M.; Manin, A.; Novoa, V.; Aranda, C. Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal. Int. J. Immunol. 2025, 13(4), 90-95. doi: 10.11648/j.iji.20251304.12

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AMA Style

Ramos SG, Villa AM, Manin A, Novoa V, Aranda C. Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal. Int J Immunol. 2025;13(4):90-95. doi: 10.11648/j.iji.20251304.12

Copy | Download

@article{10.11648/j.iji.20251304.12,
  author = {Silvia Graciela Ramos and Andrés Maria Villa and Analisa Manin and Viviana Novoa and Claudio Aranda},
  title = {Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal},
  journal = {International Journal of Immunology},
  volume = {13},
  number = {4},
  pages = {90-95},
  doi = {10.11648/j.iji.20251304.12},
  url = {https://doi.org/10.11648/j.iji.20251304.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20251304.12},
  abstract = {Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) analysis, including oligoclonal bands (OCB) and the IgG index, is central to MS diagnosis but presents technical and interpretative limitations. The kappa free light chain (κFLC) index has emerged as a promising biomarker of intrathecal immunoglobulin synthesis. Objective: To evaluate the diagnostic performance of the κFLC index in MS, determine an optimal cutoff value, and compare its accuracy with OCB detection and the IgG index. Methods: We conducted a retrospective study including 176 patients evaluated at the Neuroimmunology Laboratory of Buenos Aires, Argentina. Patients were classified into four groups: MS (n = 106), neuromyelitis optica spectrum disorders (NMOSD, n = 15), other inflammatory CNS disorders of autoimmune or infectious origin (ICNSDAI, n = 41), and paraneoplastic neurological syndromes (PNS, n = 14). κFLC, IgG, and albumin concentrations were measured in paired CSF and serum samples. The κFLC index was calculated and compared with OCB and IgG index results. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: The κFLC index was significantly higher in MS patients (median: 85; IQR: 30–305) compared with NMOSD (3.37), ICNSDAI (1.62), and PNS (1.96) groups (p < 0.0001). A κFLC index cutoff of 15 demonstrated 92% sensitivity and 83% specificity, with an area under the ROC curve of 0.952. The κFLC index correlated with the IgG index (ρ = 0.587, p < 0.0001) and OCB positivity (ρ = 0.586, p < 0.0001). κFLC index values ≥100 were observed almost exclusively in MS, with one exception in a patient with acute HSV-1 encephalitis. Conclusion: The κFLC index is a sensitive and reliable biomarker for intrathecal immunoglobulin synthesis in MS, offering advantages of automation, rapid processing, and objective quantification. External validation in independent cohorts is required before routine clinical implementation.},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Kappa Free Light Chain Index as a Diagnostic Biomarker in Multiple Sclerosis: Validation in an Argentinian Cohort and Cut off Proposal
AU  - Silvia Graciela Ramos
AU  - Andrés Maria Villa
AU  - Analisa Manin
AU  - Viviana Novoa
AU  - Claudio Aranda
Y1  - 2025/12/29
PY  - 2025
N1  - https://doi.org/10.11648/j.iji.20251304.12
DO  - 10.11648/j.iji.20251304.12
T2  - International Journal of Immunology
JF  - International Journal of Immunology
JO  - International Journal of Immunology
SP  - 90
EP  - 95
PB  - Science Publishing Group
SN  - 2329-1753
UR  - https://doi.org/10.11648/j.iji.20251304.12
AB  - Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Cerebrospinal fluid (CSF) analysis, including oligoclonal bands (OCB) and the IgG index, is central to MS diagnosis but presents technical and interpretative limitations. The kappa free light chain (κFLC) index has emerged as a promising biomarker of intrathecal immunoglobulin synthesis. Objective: To evaluate the diagnostic performance of the κFLC index in MS, determine an optimal cutoff value, and compare its accuracy with OCB detection and the IgG index. Methods: We conducted a retrospective study including 176 patients evaluated at the Neuroimmunology Laboratory of Buenos Aires, Argentina. Patients were classified into four groups: MS (n = 106), neuromyelitis optica spectrum disorders (NMOSD, n = 15), other inflammatory CNS disorders of autoimmune or infectious origin (ICNSDAI, n = 41), and paraneoplastic neurological syndromes (PNS, n = 14). κFLC, IgG, and albumin concentrations were measured in paired CSF and serum samples. The κFLC index was calculated and compared with OCB and IgG index results. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: The κFLC index was significantly higher in MS patients (median: 85; IQR: 30–305) compared with NMOSD (3.37), ICNSDAI (1.62), and PNS (1.96) groups (p < 0.0001). A κFLC index cutoff of 15 demonstrated 92% sensitivity and 83% specificity, with an area under the ROC curve of 0.952. The κFLC index correlated with the IgG index (ρ = 0.587, p < 0.0001) and OCB positivity (ρ = 0.586, p < 0.0001). κFLC index values ≥100 were observed almost exclusively in MS, with one exception in a patient with acute HSV-1 encephalitis. Conclusion: The κFLC index is a sensitive and reliable biomarker for intrathecal immunoglobulin synthesis in MS, offering advantages of automation, rapid processing, and objective quantification. External validation in independent cohorts is required before routine clinical implementation.
VL  - 13
IS  - 4
ER  -

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