ArticleAnnals of the rheumatic diseases2015
Defining the role of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) in rheumatoid arthritis through the study of PPAD biology.
Article in Annals of the rheumatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 3 of them syntheses that pooled it.
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Who cites it
67 citing papers in PubMed, 3 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- The Relationship Between Porphyromonas Gingivalis and Rheumatoid Arthritis: A Meta-Analysis.Frontiers in cellular and infection microbiology · 2022Pooled it
- Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis - a systematic review and meta-analysis.Clinical oral investigations · 2017Pooled it
- Effect of nonsurgical periodontal treatment in patients with periodontitis and rheumatoid arthritis: A systematic review.Medicina oral, patologia oral y cirugia bucal · 2016Pooled it
- Gut Microbial Functional Ecology and Microbiota-Derived Metabolites in Rheumatoid Arthritis Autoimmunity.Cells · 2026Review
- Peptidylarginine deiminase in Porphyromonas gingivalis-derived outer membrane vesicles exacerbates metabolic dysfunction-associated steatotic liver disease through the NPAS2/CYP4A10 pathway.Journal of nanobiotechnology · 2026Article
- Review
- Virulence diversity amongJournal of oral microbiology · 2026Review
- Pathogenesis ofFrontiers in cellular and infection microbiology · 2026Review
- The cross-talk between T and B lymphocytes and the oral microbiome in health and disease: a narrative review.Frontiers in immunology · 2026Review
- The Role of Oral and Gut Microbiota in Bone Health: Insights from Bacterial Extracellular Vesicles.Microorganisms · 2025Review
- Citrullination in health and disease: From physiological function to gene regulation.Genes & diseases · 2025Review
- Epidemiology and pathogenesis of the link between rheumatoid arthritis and periodontitis.Journal of Zhejiang University. Science. B · 2025Review
- Periodontopathic bacteria in rheumatoid arthritis pathogenesis: bridging clinical associations to molecular mechanisms.Frontiers in immunology · 2025Review
- Outer Membrane Vesicles Derived from Oral Bacteria Act as a Dagger in Host Immunity: Insight Tips from Local Diseases to Systemic Effects.International journal of biological sciences · 2025Review
- Review
- Oral Pathobiont-Derived Outer Membrane Vesicles in the Oral-Gut Axis.International journal of molecular sciences · 2024Review
- Periodontitis and periodontopathic bacteria as risk factors for rheumatoid arthritis: A review of the last 10 years.The Japanese dental science review · 2023Review
- An unbiased proteomic analysis of PAD4 in human monocytes: novel substrates, binding partners and subcellular localizations.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Autocitrullination confers monocyte chemotactic properties to peptidylarginine deiminase 4.Scientific reports · 2023Article
- The Interaction Effect of Anti-RgpA and Anti-PPAD Antibody Titers: An Indicator for Rheumatoid Arthritis Diagnosis.Journal of clinical medicine · 2023Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAntibodies to citrullinated proteins are a hallmark of rheumatoid arthritis (RA). Porphyromonas gingivalis peptidylarginine deiminase (PPAD) has been implicated in the initiation of RA by generating citrullinated neoantigens and due to its ability to autocitrullinate.
objectivesTo define the citrullination status and biology of PPAD in P gingivalis and to characterise the anti-PPAD antibody response in RA and associated periodontal disease (PD).
methodsPPAD in P gingivalis cells and culture supernatant were analysed by immunoblotting and mass spectrometry to detect citrullination. Recombinant PPAD (rPPAD), inactive mutant PPAD (rPPAD(C351S)), and N-terminal truncated PPAD (rPPAD(Ntx)) were cloned and expressed in Escherichia coli. Patients with RA and healthy controls were assayed for IgG antibodies to citrullinated rPPAD and unmodified rPPAD(C351S) by ELISA. Anti-PPAD antibodies were correlated with anti-cyclic citrullinated peptide (third-generation) antibody levels, RA disease activity and PD status.
resultsPPAD from P gingivalis is truncated at the N-terminal and C-terminal domains and not citrullinated. Only when artificially expressed in E coli, full-length rPPAD, but not truncated (fully active) rPPAD(Ntx), is autocitrullinated. Anti-PPAD antibodies show no heightened reactivity to citrullinated rPPAD, but are exclusively directed against the unmodified enzyme. Antibodies against PPAD do not correlate with anti-cyclic citrullinated peptide levels and disease activity in RA. By contrast, anti-PPAD antibody levels are significantly decreased in RA patients with PD.
conclusionsPPAD autocitrullination is not the underlying mechanism linking PD and RA. N-terminal processing protects PPAD from autocitrullination and enhances enzyme activity. Anti-PPAD antibodies may have a protective role for the development of PD in patients with RA.
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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.