ArticleScience translational medicine2013
Immune-mediated pore-forming pathways induce cellular hypercitrullination and generate citrullinated autoantigens in rheumatoid arthritis.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 3 of them syntheses that pooled it.
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Who cites it
146 citing papers in PubMed, 3 syntheses or guidelines pooled it, 244 citations in OpenAlex.
- Global research trends and focus on the link between rheumatoid arthritis and neutrophil extracellular traps: a bibliometric analysis from 1985 to 2023.Frontiers in immunology · 2023Pooled it
- Role of Neutrophils on the Ocular Surface.International journal of molecular sciences · 2021Pooled it
- Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases.PloS one · 2015Pooled it
- Article
- Anti-PAD4 antibodies link autoimmunity to PAD4 with CTL-associated rheumatoid arthritis.Annals of the rheumatic diseases · 2026Article
- NLRP3 inflammasome promotes PAD2/PAD4 release and protein citrullination in rheumatoid arthritis.Communications biology · 2026Article
- Differential histone tail citrullination by PAD Enzymes observed via NMR spectroscopy.bioRxiv : the preprint server for biology · 2026Article
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Roles of the Complement System in Peripheral Nerve Injury and Repair.Bioengineering (Basel, Switzerland) · 2026Review
- The role of epigenetic regulation in cuproptosis, ferroptosis and NETosis in the pathogenesis of autoimmune diseases.Apoptosis : an international journal on programmed cell death · 2025Review
- Deciphering the Structural Biology of GFAP: Connotations of Its Potency in Presaging the Diagnosis for Traumatic Brain Injury and AD.Neurology international · 2025Review
- Interplay between NETosis and the lncRNA-microRNA regulatory axis in the immunopathogenesis of cancer.Journal of physiology and biochemistry · 2025Review
- Exploring the involvement of serine proteases in neutrophil extracellular traps: a review of mechanisms and implications.Cell death & disease · 2025Review
- Role of Gut Microbiota and Metabolite Remodeling on the Development and Management of Rheumatoid Arthritis: A Narrative Review.Veterinary sciences · 2025Review
- Genomic diversity inMicrobial genomics · 2025Article
- Novel Perspectives Focused on the Relationship Between Herpesvirus Encephalitis and Anti-GFAP-Antibody-Positive Astrocytopathy.Molecular neurobiology · 2025Review
- Roles of Immunity and Endogenous Retroelements in the Pathogenesis of Rheumatoid Arthritis and Treatment Strategies.Functional & integrative genomics · 2025Review
- Investigating neutrophil responses to stimuli: Comparative analysis of reactive species-dependent and independent mechanisms.Redox biology · 2025Article
- Epidemiology and pathogenesis of the link between rheumatoid arthritis and periodontitis.Journal of Zhejiang University. Science. B · 2025Review
- The emerging role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases.MedComm · 2025Review
86 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Autoantibodies to citrullinated protein antigens are specific markers of rheumatoid arthritis (RA). Although protein citrullination can be activated by numerous stimuli in cells, it remains unclear which of these produce the prominent citrullinated autoantigens targeted in RA. In these studies, we show that RA synovial fluid cells have an unusual pattern of citrullination with marked citrullination of proteins across the broad range of molecular weights, which we term cellular hypercitrullination. Although histone citrullination is a common event during neutrophil activation and death induced by different pathways including apoptosis, NETosis, and necroptosis/autophagy, hypercitrullination is not induced by these stimuli. However, marked hypercitrullination is induced by two immune-mediated membranolytic pathways, mediated by perforin and the membrane attack complex (MAC), which are active in the RA joint and of importance in RA pathogenesis. We further demonstrate that perforin and MAC activity on neutrophils generate the profile of citrullinated autoantigens characteristic of RA. These data suggest that activation of peptidylarginine deiminases during complement and perforin activity may be at the core of citrullinated autoantigen production in RA. These pathways may be amenable to monitoring and therapeutic modulation.
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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.