ArticleJournal of neuroinflammation2024
Proteomic profile of extracellular vesicles from plasma and CSF of multiple sclerosis patients reveals disease activity-associated EAAT2.
Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Identification of diagnostic biomarkers for relapsing-remitting multiple sclerosis in plasma by mass spectrometry-based proteomics.Journal of neuropathology and experimental neurology · 2026Article
- Review
- Extracellular Vesicles From Multiple Sclerosis White Matter Exhibit Synaptic, Mitochondrial, Complement and Ageing-Related Pathway Dysregulation.Journal of extracellular vesicles · 2025Article
- Serum sEV miRNAs as Biomarkers in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.Molecular neurobiology · 2025Article
- Detection and Isolation of Tissue-Specific Extracellular Vesicles From the Blood.Journal of extracellular biology · 2025Review
- Multi-omics-driven biomarker discovery in autoimmune diseases: a comprehensive review.Frontiers in immunology · 2025Review
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Authors and funding
15 authors.
Funding
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Abstract
BACKGROUND AND
objectivesThere is an urgent need to discover blood-based biomarkers of multiple sclerosis (MS) to better define the underlying biology of relapses and monitor disease progression. The main goal of this study is to search for candidate biomarkers of MS relapses associated with circulating extracellular vesicles (EVs), an emerging tool for biomarker discovery.
methodsEVs, purified from unpaired plasma and CSF samples of RRMS patients by size-exclusion chromatography (SEC), underwent proteomic analysis to discover novel biomarkers associated with MS relapses. The candidate biomarkers of disease activity were detected by comparison approach between plasma- and CSF-EV proteomes associated with relapses. Among them, a selected potential biomarker was evaluated in a cohort of MS patients, using a novel and highly reproducible flow cytometry-based approach in order to detect low abundant EV subsets in a complex body fluid such as plasma.
resultsThe proteomic profiles of both SEC-purified plasma EVs (from 6 patients in relapse and 5 patients in remission) and SEC-purified CSF EVs (from 4 patients in relapse and 3 patients in remission) revealed a set of proteins associated with MS relapses significant enriched in the synaptic transmission pathway. Among common proteins, excitatory amino-acid transporter 2, EAAT2, responsible for the majority of the glutamate uptake in CNS, was worthy of further investigation. By screening plasma samples from 110 MS patients, we found a significant association of plasma EV-carried EAAT2 protein (EV-EAAT2) with MS relapses, regardless of disease-modifying therapies. This finding was confirmed by investigating the presence of EV-EAAT2 in plasma samples collected longitudinally from 10 RRMS patients, during relapse and remission. Moreover, plasma EV-EAAT2 levels correlated positively with Expanded Disability Status Scale (EDSS) score in remitting MS patients but showed a negative correlation with age in patients with secondary progressive (SPMS).
conclusionOur results emphaticize the usefulness of plasma EVs as a source of accessible biomarkers to remotely analyse the CNS status. Plasma EV-EAAT2 showed to be a promising biomarker for MS relapses. Further studies are required to assess the clinical relevance of this biomarker also for disability progression independent of relapse activity and transition from RRMS towards SPMS.
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