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Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study
BACKGROUND AND OBJECTIVES: Kappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFL...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663206/ https://www.ncbi.nlm.nih.gov/pubmed/36376096 http://dx.doi.org/10.1212/NXI.0000000000200049 |
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author | Levraut, Michael Laurent-Chabalier, Sabine Ayrignac, Xavier Bigaut, Kévin Rival, Manon Squalli, Sanae Zéphir, Hélène Alberto, Tifanie Pekar, Jean-David Ciron, Jonathan Biotti, Damien Puissant-Lubrano, Bénédicte Camdessanché, Jean-Philippe Tholance, Yannick Casez, Olivier Toussaint, Bertrand Marion, Jeanne Moreau, Thibault Lakomy, Daniela Thomasset, Audrey Maillart, Elisabeth Sterlin, Delphine Maurousset, Aude Rocher, Auriane Laplaud, David Axel Bigot-Corbel, Edith Bertho, Pierre-Olivier Pelletier, Jean Boucraut, Joseph Labauge, Pierre Vincent, Thierry De Sèze, Jérôme Jahn, Isabelle Seitz-Polski, Barbara Thouvenot, Eric Lebrun-Frenay, Christine |
author_facet | Levraut, Michael Laurent-Chabalier, Sabine Ayrignac, Xavier Bigaut, Kévin Rival, Manon Squalli, Sanae Zéphir, Hélène Alberto, Tifanie Pekar, Jean-David Ciron, Jonathan Biotti, Damien Puissant-Lubrano, Bénédicte Camdessanché, Jean-Philippe Tholance, Yannick Casez, Olivier Toussaint, Bertrand Marion, Jeanne Moreau, Thibault Lakomy, Daniela Thomasset, Audrey Maillart, Elisabeth Sterlin, Delphine Maurousset, Aude Rocher, Auriane Laplaud, David Axel Bigot-Corbel, Edith Bertho, Pierre-Olivier Pelletier, Jean Boucraut, Joseph Labauge, Pierre Vincent, Thierry De Sèze, Jérôme Jahn, Isabelle Seitz-Polski, Barbara Thouvenot, Eric Lebrun-Frenay, Christine |
author_sort | Levraut, Michael |
collection | PubMed |
description | BACKGROUND AND OBJECTIVES: Kappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS. METHODS: We conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC). RESULTS: One thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p = 0.123 and p = 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p < 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p < 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p = 0.065). In the multivariate analysis model, female gender (p = 0.003), young age (p = 0.013), and evidence of disease activity (p < 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index. DISCUSSION: KFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders. |
format | Online Article Text |
id | pubmed-9663206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-96632062022-11-14 Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study Levraut, Michael Laurent-Chabalier, Sabine Ayrignac, Xavier Bigaut, Kévin Rival, Manon Squalli, Sanae Zéphir, Hélène Alberto, Tifanie Pekar, Jean-David Ciron, Jonathan Biotti, Damien Puissant-Lubrano, Bénédicte Camdessanché, Jean-Philippe Tholance, Yannick Casez, Olivier Toussaint, Bertrand Marion, Jeanne Moreau, Thibault Lakomy, Daniela Thomasset, Audrey Maillart, Elisabeth Sterlin, Delphine Maurousset, Aude Rocher, Auriane Laplaud, David Axel Bigot-Corbel, Edith Bertho, Pierre-Olivier Pelletier, Jean Boucraut, Joseph Labauge, Pierre Vincent, Thierry De Sèze, Jérôme Jahn, Isabelle Seitz-Polski, Barbara Thouvenot, Eric Lebrun-Frenay, Christine Neurol Neuroimmunol Neuroinflamm Research Article BACKGROUND AND OBJECTIVES: Kappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS. METHODS: We conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC). RESULTS: One thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (p = 0.123 and p = 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (p < 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (p < 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (p = 0.065). In the multivariate analysis model, female gender (p = 0.003), young age (p = 0.013), and evidence of disease activity (p < 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index. DISCUSSION: KFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders. Lippincott Williams & Wilkins 2022-11-14 /pmc/articles/PMC9663206/ /pubmed/36376096 http://dx.doi.org/10.1212/NXI.0000000000200049 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Research Article Levraut, Michael Laurent-Chabalier, Sabine Ayrignac, Xavier Bigaut, Kévin Rival, Manon Squalli, Sanae Zéphir, Hélène Alberto, Tifanie Pekar, Jean-David Ciron, Jonathan Biotti, Damien Puissant-Lubrano, Bénédicte Camdessanché, Jean-Philippe Tholance, Yannick Casez, Olivier Toussaint, Bertrand Marion, Jeanne Moreau, Thibault Lakomy, Daniela Thomasset, Audrey Maillart, Elisabeth Sterlin, Delphine Maurousset, Aude Rocher, Auriane Laplaud, David Axel Bigot-Corbel, Edith Bertho, Pierre-Olivier Pelletier, Jean Boucraut, Joseph Labauge, Pierre Vincent, Thierry De Sèze, Jérôme Jahn, Isabelle Seitz-Polski, Barbara Thouvenot, Eric Lebrun-Frenay, Christine Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study |
title | Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study |
title_full | Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study |
title_fullStr | Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study |
title_full_unstemmed | Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study |
title_short | Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study |
title_sort | kappa free light chain biomarkers are efficient for the diagnosis of multiple sclerosis: a large multicenter cohort study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663206/ https://www.ncbi.nlm.nih.gov/pubmed/36376096 http://dx.doi.org/10.1212/NXI.0000000000200049 |
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