Rosenstein, Igal;
Axelsson, Markus;
Novakova, Lenka;
Rasch, Sofia;
Blennow, Kaj;
Zetterberg, Henrik;
Lycke, Jan;
(2023)
High levels of kappa free light chain synthesis predict cognitive decline in relapsing-remitting multiple sclerosis.
Frontiers in Immunology
, 14
, Article 1106028. 10.3389/fimmu.2023.1106028.
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Abstract
BACKGROUND: Evolving evidence suggests that measurement of cerebrospinal fluid (CSF) kappa free light chain (KFLC) synthesis has high diagnostic sensitivity and specificity for multiple sclerosis (MS), but its prognostic ability is less investigated. The usefulness of KFLC in predicting cognitive impairment (CI) is still unknown. METHODS: In a monocentric longitudinal retrospecitve cohort study, KFLC-index ([CSF KFLC/serum KFLC]/[CSF albumin/serum albumin]) measured by latex-enhanced immunonephelometry was prospectively determined as part of the diagnostic workup in patients with early relapsing-remitting MS (RRMS, n=77). The ability of KFLC-index to predict information processing speed (IPS) worsening as assessed with the symbol digit modalities test (SDMT) was investigated in univariable and multivariable models. RESULTS: In patients with KFLC-index>100 (n=31), 11 subjects (35.5%) showed reduced SDMT scores by ≥8 points at follow-up (mean follow-up time 7.3 ± 2.6 years), compared with their baseline scores (p=0.01). Baseline KFLC-index>100 was strongly associated with a higher hazard of SDMT score reduction at follow-up (adjusted hazard ratio 10.5, 95% confidence interval 2.2-50.8, p=0.003; median time to SDMT reduction 7 years). CONCLUSION: Intrathecal KFLC synthesis has become an attractive diagnostic tool for MS. We show for the first time that in a real-world setting of early RRMS, KFLC-index predicted cognitive decline. Whether this predictive ability of KFLC-index also concerns other cognitive domains than IPS, warrants further investigations.
| Type: | Article |
|---|---|
| Title: | High levels of kappa free light chain synthesis predict cognitive decline in relapsing-remitting multiple sclerosis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2023.1106028 |
| Publisher version: | https://doi.org/10.3389/fimmu.2023.1106028 |
| Language: | English |
| Additional information: | Copyright © 2023 Rosenstein, Axelsson, Novakova, Rasch, Blennow, Zetterberg and Lycke. 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) and the copyright owner(s) 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. |
| Keywords: | biomarkers, cognitive impairment (CI), kappa free light chains, multiple sclerosis, symbol digit modalities test (SDMT), Humans, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Cohort Studies, Immunoglobulin kappa-Chains, Cognitive Dysfunction |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10164645 |
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