ArticleArthritis and rheumatism2010
Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis.
Article in Arthritis and rheumatism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 329 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
329 citing papers in PubMed, 3 syntheses or guidelines pooled it, 647 citations in OpenAlex.
- The Relationship Between Porphyromonas Gingivalis and Rheumatoid Arthritis: A Meta-Analysis.Frontiers in cellular and infection microbiology · 2022Pooled it
- Pooled it
- Association between anti-Porphyromonas gingivalis antibody, anti-citrullinated protein antibodies, and rheumatoid arthritis : A meta-analysis.Zeitschrift fur Rheumatologie · 2018Pooled it
- Dysbiosis-Mediated Inflammation: A Pathophysiological Link Between Rheumatoid Arthritis and Periodontitis.Journal of clinical periodontology · 2026Trial
- Effects of non-surgical periodontal therapy on periodontal laboratory and clinical data as well as on disease activity in patients with rheumatoid arthritis.Clinical oral investigations · 2019Trial
- Mapping scientific knowledge on the association between periodontal disease and rheumatoid arthritis: A bibliometric and altmetric analysis of the 100 most-cited articles.Medicina oral, patologia oral y cirugia bucal · 2026Review
- Advanced Biological Therapies: Principles, Mechanisms and Medical Applications.Journal of clinical medicine · 2026Review
- Anti-Modified Protein Antibodies in Rheumatoid Arthritis: Pathogenic, Protective, or Passive Bystander?Immunological reviews · 2026Review
- Pathogens in rheumatoid arthritis: epidemiological, mechanistic, and clinical insights.Biomarker research · 2026Review
- Intestinal microbiota and arthritis.EULAR rheumatology open · 2026Review
- Association of a Novel Dietary Index Assessing Gut Microbiota Impact With Rheumatoid Arthritis: A Nationwide Population-Based Study.Food science & nutrition · 2026Article
- Preclinical Rheumatoid Arthritis: Pathogenesis, Risk Stratification, and Therapeutic Interception.Journal of clinical medicine · 2026Review
- Histological analysis of periodontal tissues in patients with autoimmune diseases: a comparative cross-sectional study of inflammatory cell infiltration and epithelial barrier function.BMC oral health · 2026Article
- Multi-omics analysis of associations between host demographics and saliva metabolome, sugar profiles, and microbiome profiles.Scientific reports · 2026Article
- Plasmablast Storms: Microbial Drivers of Acute and Chronic Autoimmune Flares.Microorganisms · 2026Review
- Trained immunity as a systemic bridge: the liver-gut-immune-oral axis in the comorbidity of chronic liver disease and periodontitis.Frontiers in immunology · 2026Review
- Host-driven citrullination of extracellular vesicle-derived microbial proteins linksJournal of oral microbiology · 2026Article
- Oral health status and subgingival microbiota in children with juvenile idiopathic arthritis.Frontiers in cellular and infection microbiology · 2026Article
- Immunological cross-talk between periodontitis and systemic lupus erythematosus: the role of T-B cell dysregulation in the shared pathogenic network.Frontiers in immunology · 2026Review
- The cross-talk between T and B lymphocytes and the oral microbiome in health and disease: a narrative review.Frontiers in immunology · 2026Review
269 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 5 countries.
Funding
Abstract
objectiveTo investigate protein citrullination by the periodontal pathogen Porphyromonas gingivalis as a potential mechanism for breaking tolerance to citrullinated proteins in rheumatoid arthritis (RA).
methodsThe expression of endogenous citrullinated proteins was analyzed by immunoblotting of cell extracts from P gingivalis and 10 other oral bacteria. P gingivalis-knockout strains lacking the bacterial peptidylarginine deiminases (PADs) or gingipains were created to assess the role of these enzymes in citrullination. Citrullination of human fibrinogen and α-enolase by P gingivalis was studied by incubating live wild-type and knockout strains with the proteins and analyzing the products by immunoblotting and mass spectrometry.
resultsEndogenous protein citrullination was abundant in P gingivalis but lacking in the other oral bacteria. Deletion of the bacterial PAD gene resulted in complete abrogation of protein citrullination. Inactivation of arginine gingipains, but not lysine gingipains, led to decreased citrullination. Incubation of wild-type P gingivalis with fibrinogen or α-enolase caused degradation of the proteins and citrullination of the resulting peptides at carboxy-terminal arginine residues, which were identified by mass spectrometry.
conclusionOur findings demonstrate that among the oral bacterial pathogens tested, P gingivalis is unique in its ability to citrullinate proteins. We further show that P gingivalis rapidly generates citrullinated host peptides by proteolytic cleavage at Arg-X peptide bonds by arginine gingipains, followed by citrullination of carboxy-terminal arginines by bacterial PAD. Our results suggest a novel model where P gingivalis-mediated citrullination of bacterial and host proteins provides a molecular mechanism for generating antigens that drive the autoimmune response in RA.
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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.