Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis
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Published:2023-11-08
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Volume:
Page:jnnp-2023-332251
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ISSN:0022-3050
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Container-title:Journal of Neurology, Neurosurgery & Psychiatry
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language:en
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Short-container-title:J Neurol Neurosurg Psychiatry
Author:
Fissolo Nicolás, Benkert Pascal, Sastre-Garriga JaumeORCID, Mongay-Ochoa Neus, Vilaseca-Jolonch Andreu, Llufriu SaraORCID, Blanco Yolanda, Hegen HaraldORCID, Berek Klaus, Perez-Miralles Francisco, Rejdak Konrad, Villar Luisa M, Monreal EnricORCID, Alvarez-Lafuente RobertoORCID, Soylu Onder K, Abdelhak Ahmed, Bachhuber Franziska, Tumani HayrettinORCID, Martínez-Yélamos Sergio, Sánchez-López Antonio J, García-Merino Antonio, Gutiérrez Lucía, Castillo-Trivino TamaraORCID, Lycke JanORCID, Rosenstein IgalORCID, Furlan Roberto, Filippi MassimoORCID, Téllez Nieves, Ramió-Torrentà Lluís, Lünemann Jan DORCID, Wiendl Heinz, Eichau Sara, Khalil MichaelORCID, Kuhle Jens, Montalban Xavier, Comabella ManuelORCID
Abstract
BackgroundWe aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).MethodsA total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman’s r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods.ResultsMedian (IQR) age of patients was 52.9 (46.4–58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0–12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change.ConclusionsLevels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.
Subject
Psychiatry and Mental health,Neurology (clinical),Surgery
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