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Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis
BACKGROUND: While kappa free light chain (KFLC) index has become a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. B cells play a crucial role in MS pathogenesis, but the impact from increased intrathecal production of immunoglobulins and KFLC rem...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511607/ https://www.ncbi.nlm.nih.gov/pubmed/37314506 http://dx.doi.org/10.1007/s00415-023-11817-9 |
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author | Rosenstein, Igal Axelsson, Markus Novakova, Lenka Malmeström, Clas Blennow, Kaj Zetterberg, Henrik Lycke, Jan |
author_facet | Rosenstein, Igal Axelsson, Markus Novakova, Lenka Malmeström, Clas Blennow, Kaj Zetterberg, Henrik Lycke, Jan |
author_sort | Rosenstein, Igal |
collection | PubMed |
description | BACKGROUND: While kappa free light chain (KFLC) index has become a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. B cells play a crucial role in MS pathogenesis, but the impact from increased intrathecal production of immunoglobulins and KFLC remains to be determined. Recently, it has become evident that insidious worsening is not confined to progressive MS but is also common in relapsing–remitting MS (RRMS), a feature known as progression independent of relapse activity (PIRA). METHODS: We retrospectively identified 131 patients with clinically isolated syndrome or early RRMS who had determined KFLC index as part of their diagnostic workup. Demographic and clinical data were extracted from the Swedish MS registry. Associations of baseline KFLC index with evidence of disease activity (EDA) and PIRA were investigated in multivariable cox proportional hazards regression models. RESULTS: KFLC index was significantly higher in PIRA (median 148.5, interquartile range [IQR] 106.9–253.5) compared with non-PIRA (78.26, IQR 28.93–186.5, p = 0.009). In a multivariable cox regression model adjusted for confounders, KFLC index emerged as an independent risk factor for PIRA (adjusted hazard ratio [aHR] 1.005, 95% confidence interval [CI] 1.002–1.008, p = 0.002). Dichotomized by the cut-off value KFLC index > 100, patients with KFLC index > 100 had an almost fourfold increase in the risk for developing PIRA. KFLC index was also predictive of evidence of disease activity during follow-up. CONCLUSIONS: Our data indicate that high KFLC index at baseline is predictive of PIRA, EDA-3, and overall worse prognosis in MS. |
format | Online Article Text |
id | pubmed-10511607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-105116072023-09-22 Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis Rosenstein, Igal Axelsson, Markus Novakova, Lenka Malmeström, Clas Blennow, Kaj Zetterberg, Henrik Lycke, Jan J Neurol Original Communication BACKGROUND: While kappa free light chain (KFLC) index has become a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. B cells play a crucial role in MS pathogenesis, but the impact from increased intrathecal production of immunoglobulins and KFLC remains to be determined. Recently, it has become evident that insidious worsening is not confined to progressive MS but is also common in relapsing–remitting MS (RRMS), a feature known as progression independent of relapse activity (PIRA). METHODS: We retrospectively identified 131 patients with clinically isolated syndrome or early RRMS who had determined KFLC index as part of their diagnostic workup. Demographic and clinical data were extracted from the Swedish MS registry. Associations of baseline KFLC index with evidence of disease activity (EDA) and PIRA were investigated in multivariable cox proportional hazards regression models. RESULTS: KFLC index was significantly higher in PIRA (median 148.5, interquartile range [IQR] 106.9–253.5) compared with non-PIRA (78.26, IQR 28.93–186.5, p = 0.009). In a multivariable cox regression model adjusted for confounders, KFLC index emerged as an independent risk factor for PIRA (adjusted hazard ratio [aHR] 1.005, 95% confidence interval [CI] 1.002–1.008, p = 0.002). Dichotomized by the cut-off value KFLC index > 100, patients with KFLC index > 100 had an almost fourfold increase in the risk for developing PIRA. KFLC index was also predictive of evidence of disease activity during follow-up. CONCLUSIONS: Our data indicate that high KFLC index at baseline is predictive of PIRA, EDA-3, and overall worse prognosis in MS. Springer Berlin Heidelberg 2023-06-14 2023 /pmc/articles/PMC10511607/ /pubmed/37314506 http://dx.doi.org/10.1007/s00415-023-11817-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Communication Rosenstein, Igal Axelsson, Markus Novakova, Lenka Malmeström, Clas Blennow, Kaj Zetterberg, Henrik Lycke, Jan Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis |
title | Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis |
title_full | Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis |
title_fullStr | Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis |
title_full_unstemmed | Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis |
title_short | Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis |
title_sort | intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis |
topic | Original Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511607/ https://www.ncbi.nlm.nih.gov/pubmed/37314506 http://dx.doi.org/10.1007/s00415-023-11817-9 |
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