ArticleNeurology(R) neuroimmunology & neuroinflammation2025
Aberrant Complement Activation Is Associated With Structural Brain Damage 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 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Crossroads of Neuroinflammation and Biomarkers in Multiple Sclerosis: A Systematic Review.Cells · 2026Pooled it
- Role of complement and complement-targeted therapeutics in neurological diseases.Nature reviews. Neurology · 2026Review
- CSF1R inhibition following antibody mediated demyelination has limited impact on remyelination.Acta neuropathologica communications · 2026Article
- The complement system in Alzheimer's disease: evaluating biomarker potential in a complex neuroimmune context.Journal of neuroinflammation · 2026Review
- Emerging CSF and Serum Biomarkers in Multiple Sclerosis: Cytokines, MOG, GFAP, and Beyond.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Granulocyte and astrocyte markers distinguish MOG-antibody disease and neuromyelitis optica from multiple sclerosis.Brain : a journal of neurology · 2026Observational
- Transcriptome analysis of the prefrontal cortex identifies inflammatory genes associated with cognitive impairment in a model of multiple sclerosis.Cell death discovery · 2026Article
- Aberrant Complement Activation Is a Prominent Feature of Chronic Inflammatory Demyelinating Polyneuropathy.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Characteristic patterns of complement deposition in NMOSD, MOGAD, and MS.Acta neuropathologica · 2026Article
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Maintenance of chronic neuroinflammation in multiple sclerosis via interferon signaling and CD8 T-cell-mediated cytotoxicity.Research square · 2025Article
- Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis.International journal of molecular sciences · 2025Observational
- Brain and Immune System: Intercellular Communication During Homeostasis and Neuroimmunomodulation upon Dysfunction.International journal of molecular sciences · 2025Review
- CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New-Onset Refractory Status Epilepticus.Annals of clinical and translational neurology · 2025Article
Corrections and comments
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Authors and funding
39 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesLevels of activated complement proteins in the CSF are increased in people with multiple sclerosis (MS) and are associated with clinical disease severity. In this study, we determined whether complement activation profiles track with quantitative MRI metrics and liquid biomarkers indicative of disease activity and progression.
methodsComplement components and activation products (Factor H and I, C1q, C3, C4, C5, Ba, Bb, C3a, C4a, C5a, and sC5b-9) and liquid biomarkers (neurofilament light chain, glial fibrillary acidic protein [GFAP], CXCL-13, CXCL-9, and IL-12b) were quantified in the CSF of 112 patients with clinically isolated syndromes and 127 patients with MS; longitudinal MRIs according to a standardized protocol of the Swiss MS cohort were assessed. We used multivariable models to analyze associations of the 12 complement parameters as individual independent variables and longitudinal brain volumes, T2-weighted (T2w) lesion volumes, contrast-enhancing (CELs) and paramagnetic rim lesions (PRLs), and molecular biomarkers as dependent variables, respectively.
resultsStrongest associations with accelerated brain atrophy were found for C4a: doubling of C4a CSF levels was associated with an additional brain volume loss of -0.24% (95% CI -0.31% to -0.16%; DISCUSSION: Intrathecal complement activation is consistently associated with MRI metrics and liquid biomarkers indicative for MS disease activity and progression. Our results demonstrate that aberrant complement activation is strongly associated with structural brain damage in MS. Therapeutic targeting of the complement system might limit disability accumulation due to MS.
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