Trial reportMultiple sclerosis and related disorders2019
Cerebrospinal fluid biomarkers link toxic astrogliosis and microglial activation to multiple sclerosis severity.
Trial report in Multiple sclerosis and related disorders, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04496830 (Cerebrospinal Fluid-biomarkers-based Diagnostic and Prognostic Models for Multiple Sclerosis), which is not on this map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Cerebrospinal Fluid-biomarkers-based Diagnostic and Prognostic Models for Multiple Sclerosis
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Roles of neuropathology-associated reactive astrocytes: a systematic review.Acta neuropathologica communications · 2023Pooled it
- CSF Leukocytes in Intracranial Infections: Diagnostic, Mechanistic, and Therapeutic Insights for Neurocritical Care.Cellular and molecular neurobiology · 2026Review
- Inflammatory microglia signals drive A1-like polarization of astrocytes even in the presence of HIV-1 Tat.Molecular neurobiology · 2025Article
- Profiling the Cerebrospinal Fluid Proteome in Progressive Multiple Sclerosis: Treatment Effects and Associations with IgM Oligoclonal Bands.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- SERPINA3 predicts long-term neurological outcomes and mortality in patients with intracerebral hemorrhage.Cell death & disease · 2025Article
- Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect clinical and radiographic disease activity in multiple sclerosis.Nature communications · 2024Article
- Possible Roles of Extracellular Vesicles in the Pathogenesis and Interventions of Immune-Mediated Central Demyelinating Diseases.Experimental neurobiology · 2024Review
- Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis.Neural regeneration research · 2024Review
- Microglial ferroptotic stress causes non-cell autonomous neuronal death.Molecular neurodegeneration · 2024Article
- Recommendations for reproducibility of cerebrospinal fluid extracellular vesicle studies.Journal of extracellular vesicles · 2024Review
- Tonabersat Significantly Reduces Disease Progression in an Experimental Mouse Model of Multiple Sclerosis.International journal of molecular sciences · 2023Article
- CDP-choline to promote remyelination in multiple sclerosis: the need for a clinical trial.Neural regeneration research · 2023Review
- Early urinary candidate biomarkers and clinical outcomes of intervention in a rat model of experimental autoimmune encephalomyelitis.Royal Society open science · 2023Article
- The application of Aptamer in biomarker discovery.Biomarker research · 2023Review
- Immune profiling in multiple sclerosis: a single-center study of 65 cytokines, chemokines, and related molecules in cerebrospinal fluid and serum.Frontiers in immunology · 2023Article
- Molecular models of multiple sclerosis severity identify heterogeneity of pathogenic mechanisms.Nature communications · 2022Article
- Minocycline treatment in clinically isolated syndrome and serum NfL, GFAP, and metalloproteinase levels.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Article
- The role of glial cells in multiple sclerosis disease progression.Nature reviews. Neurology · 2022Review
- Drug library screen identifies inhibitors of toxic astrogliosis.Multiple sclerosis and related disorders · 2022Article
- Aptamer Applications in Neuroscience.Pharmaceuticals (Basel, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundOnce multiple sclerosis (MS) reaches the progressive stage, immunomodulatory treatments have limited efficacy. This suggests that processes other than activation of innate immunity may at least partially underlie disability progression during late stages of MS. Pathology identified these alternative processes as aberrant activation of astrocytes and microglia, and subsequent degeneration of oligodendrocytes and neurons. However, we mostly lack biomarkers that could measure central nervous system (CNS) cell-specific intrathecal processes in living subjects. This prevents differentiating pathogenic processes from an epiphenomenon. Therefore, we sought to develop biomarkers of CNS cell-specific processes and link them to disability progression in MS.
methodsIn a blinded manner, we measured over 1000 proteins in the cerebrospinal fluid (CSF) of 431 patients with neuroimmunological diseases and healthy volunteers using modified DNA-aptamers (SOMAscan®). We defined CNS cell type-enriched clusters using variable cluster analysis, combined with in vitro modeling. Differences between diagnostic categories were identified in the training cohort (n = 217) and their correlation to disability measures were assessed; results were validated in an independent validation cohort (n = 214).
resultsAstrocyte cluster 8 (MMP7, SERPINA3, GZMA and CLIC1) and microglial cluster 2 (DSG2 and TNFRSF25) were reproducibly elevated in MS and had a significant and reproducible correlation with MS severity suggesting their pathogenic role. In vitro studies demonstrated that proteins of astrocyte cluster 8 are noticeably released upon stimulation with proinflammatory stimuli and overlap with the phenotype of recently described neuro-toxic (A1) astrocytes.
conclusionMicroglial activation and toxic astrogliosis are associated with MS disease process and may partake in CNS tissue destruction. This hypothesis should be tested in new clinical trials.
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