ArticleCell death & disease2023
Multiple sclerosis plasma IgG aggregates induce complement-dependent neuronal apoptosis.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Multiple Sclerosis and Viruses: « Liaisons Dangereuses ».Reviews in medical virology · 2026Review
- Mitochondria-associated endoplasmic reticulum membranes and calcium ion exchange: A novel direction for aging and neurodegenerative diseases.Neural regeneration research · 2026Article
- Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.Neurobiology of disease · 2026Article
- Multiplex Detection of Immunoglobulins Uncovers Intrathecal IgA Elevation in Multiple Sclerosis.Cells · 2026Article
- Sialylation in the nervous system: Functions and mechanisms.The Journal of biological chemistry · 2026Review
- Autoimmune neuroinflammation leads to neuronal death via MIF nuclease-mediated parthanatos.Nature neuroscience · 2026Article
- CNS-compartmentalized IgG aggregates and glycosylation in multiple sclerosis contribute to oligoclonal bands and neuronal cytotoxicity.Frontiers in immunology · 2026Article
- Protective Effects of Heat-Killed Lactobacilli against Plasma-Induced Neurotoxicity in Multiple Sclerosis.Probiotics and antimicrobial proteins · 2025Article
- Overview of Metformin and Neurodegeneration: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- IgG Biomarkers in Multiple Sclerosis: Deciphering Their Puzzling Protein A Connection.Biomolecules · 2025Review
- From diagnosis to treatment: exploring the mechanisms underlying optic neuritis in multiple sclerosis.Journal of translational medicine · 2025Review
- HERV-W Env Induces Neuron Pyroptosis via the NLRP3-CASP1-GSDMD Pathway in Recent-Onset Schizophrenia.International journal of molecular sciences · 2025Article
- The Compelling Role of Brain-Derived Neurotrophic Factor Signaling in Multiple Sclerosis: Role of BDNF Activators.CNS neuroscience & therapeutics · 2024Review
- Immunoglobulin G and Complement as Major Players in the Neurodegeneration of Multiple Sclerosis.Biomolecules · 2024Review
- The complement system in neurodegenerative and inflammatory diseases of the central nervous system.Frontiers in neurology · 2024Review
- The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis.Journal of immunology research · 2024Review
- The elusive nature of the oligoclonal bands in multiple sclerosis.Journal of neurology · 2024Review
- Plasma IgG aggregates as biomarkers for multiple sclerosis.Clinical immunology (Orlando, Fla.) · 2023Article
- Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels.Current issues in molecular biology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Grey matter pathology is central to the progression of multiple sclerosis (MS). We discovered that MS plasma immunoglobulin G (IgG) antibodies, mainly IgG1, form large aggregates (>100 nm) which are retained in the flow-through after binding to Protein A. Utilizing an annexin V live-cell apoptosis detection assay, we demonstrated six times higher levels of neuronal apoptosis induced by MS plasma IgG aggregates (n = 190, from two cohorts) compared to other neurological disorders (n = 116) and healthy donors (n = 44). MS IgG aggregate-mediated, complement-dependent neuronal apoptosis was evaluated in multiple model systems including primary human neurons, primary human astrocytes, neuroblastoma SH-SY5Y cells, and newborn mouse brain slices. Immunocytochemistry revealed the co-deposition of IgG, early and late complement activation products (C1q, C3b, and membrane attack complex C5b9), as well as active caspase 3 in treated neuronal cells. Furthermore, we found that MS plasma cytotoxic antibodies are not present in Protein G flow-through, nor in the paired plasma. The neuronal apoptosis can be inhibited by IgG depletion, disruption of IgG aggregates, pan-caspase inhibitor, and is completely abolished by digestion with IgG-cleaving enzyme IdeS. Transmission electron microscopy and nanoparticle tracking analysis revealed the sizes of MS IgG aggregates are greater than 100 nm. Our data support the pathological role of MS IgG antibodies and corroborate their connection to complement activation and axonal damage, suggesting that apoptosis may be a mechanism of neurodegeneration in MS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.