ArticleNeurology(R) neuroimmunology & neuroinflammation2025
Proteomics Reveals Age as Major Modifier of Inflammatory CSF Signatures in Multiple Sclerosis.
Article in Neurology(R) neuroimmunology & neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Cerebrospinal Fluid sCD27 as a Biomarker of Neuroinflammatory Disease: A Systematic Review and Meta-Analysis.Journal of neurochemistry · 2026Pooled it
- Comprehensive Meta-Analysis of Differentially Expressed Proteins in Cerebrospinal Fluid Associated with Multiple Sclerosis.International journal of molecular sciences · 2025Pooled it
- Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.International journal of molecular sciences · 2026Article
- Proteomic Profiling of Optic Nerves From SMOX-Deficient Mice Identifies Regulators of Neuroinflammation and Axonal Damage in Optic Neuritis.Investigative ophthalmology & visual science · 2026Article
- Multi-omics integration provides biological insight and prioritizes potential drug targets in multiple sclerosis progression.Journal of neuroinflammation · 2026Article
- CSF κ-Free light chain index in suspected multiple sclerosis: diagnostic performance vs. Oligoclonal bands and alignment with 2017/2024 McDonald criteria.Acta neurologica Belgica · 2026Article
- Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.EBioMedicine · 2026Article
- A CSF disease-associated macrophage signature defines progressive multiple sclerosis.Journal of neuroinflammation · 2026Article
- Proteomics signatures associated with cognitive trajectories: evidence from the English Longitudinal Study of Ageing.medRxiv : the preprint server for health sciences · 2026Article
- Pregnancy quenches inflammation through neuroimmune crosstalk.Nature immunology · 2026Article
- Modulation of the immunological and neuroinflammatory microenvironment in older people with multiple sclerosis.Frontiers in immunology · 2026Review
- Residual inflammation in the cerebrospinal fluid after short- and long-term natalizumab treatment in relapsing-remitting multiple sclerosis.Frontiers in immunology · 2026Observational
- A novel multiplexed biomarker panel reveals key molecular pathways in progressive multiple sclerosis.Brain communications · 2026Article
- Biomarker discovery using NUcleic Acid-Linked Immuno-Sandwich Assay in multiple sclerosis patients experiencing progression independent of relapse activity.Multiple sclerosis (Houndmills, Basingstoke, England) · 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
- The diagnostic potential of proteomics and machine learning in Lyme neuroborreliosis.Nature communications · 2025Article
- Proteomic Profiling and Pathophysiological Implications in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Multi-omics-driven biomarker discovery in autoimmune diseases: a comprehensive review.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesMultiple sclerosis (MS) can start as relapsing or progressive. While their clinical features and treatment responses are distinct, it has remained uncertain whether their pathomechanisms differ. A notable age-related effect on MS phenotype and response to immunotherapies is well acknowledged, but the underlying pathophysiologic reasons are yet to be fully elucidated. We aimed to identify disease-specific and age-related proteomic signatures using a comprehensive targeted proteomic analysis.
methodsIn our retrospective cohort study, we analyzed the CSF and serum proteome of age-matched individuals with treatment-naïve relapsing-remitting and primary progressive MS, neurologic controls (NC), and individuals with neuroborreliosis using targeted proteomics and validated findings in an independent cohort. Proteomic results were integrated with clinical and laboratory covariates.
resultsAmong 2,500 proteins, 47 CSF proteins were distinct between individuals with MS (n = 60) and NC (n = 20), with a subset also differing from those with neuroborreliosis (n = 8). We identified MS-associated proteins, including novel candidate biomarkers such as LY9 and JCHAIN, and putative treatment targets, such as SLAMF7, BCMA, and IL5RA, for which drugs are already licensed in other indications. The CSF proteome differences between relapsing and progressive MS were minimal, but major changes were noted in individuals older than 50 years, indicating a shift from MS-associated inflammatory to age-related protein signature. NEFL was the only serum protein that differed between individuals with MS and controls. DISCUSSION: This study unveils a unique CSF proteomic signature in MS, providing new pathophysiologic insights and identifying novel biomarker candidates and potential therapeutic targets. Our findings highlight similar immunologic mechanisms in relapsing and progressive MS and underscore aging's profound effect on the intrathecal immune response. This aligns with the observed lower efficacy of immunotherapies in the elderly, thus emphasizing the necessity for alternative therapeutic approaches in treating individuals with MS beyond the age of 50.
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