ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Autoantibodies From Single Circulating Plasmablasts React With Citrullinated Antigens and Porphyromonas gingivalis in Rheumatoid Arthritis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- 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
- Periodontitis and periodontopathic bacteria as risk factors for rheumatoid arthritis: A review of the last 10 years.The Japanese dental science review · 2023Review
- Article
- Characteristics of the (Auto)Reactive T Cells in Rheumatoid Arthritis According to the Immune Epitope Database.International journal of molecular sciences · 2023Review
- Positive Effects of Biologics on Osteoporosis in Rheumatoid Arthritis.Journal of rheumatic diseases · 2023Review
- Anti-Citrullinated Peptide Antibodies Control OralInternational journal of molecular sciences · 2022Article
- Integrated single cell and spatial transcriptomics reveal autoreactive differentiated B cells in joints of early rheumatoid arthritis.Scientific reports · 2022Article
- Effects of Biological/Targeted Therapies on Bone Mineral Density in Inflammatory Arthritis.International journal of molecular sciences · 2022Review
- Outer membrane vesicles of the oral pathogenFrontiers in oral health · 2022Article
- Disease mechanisms in preclinical rheumatoid arthritis: A narrative review.Frontiers in medicine · 2022Review
- Antibodies to a CitrullinatedFrontiers in immunology · 2022Article
- Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing on Citrullination, Carbamylation, and Acetylation.International journal of molecular sciences · 2021Review
- The Germinal Center Milieu in Rheumatoid Arthritis: The Immunological Drummer or Dancer?International journal of molecular sciences · 2021Review
- B cells in rheumatoid arthritis synovial tissues encode focused antibody repertoires that include antibodies that stimulate macrophage TNF-α production.Clinical immunology (Orlando, Fla.) · 2020Article
- Iguratimod dose dependently inhibits the expression of citrullinated proteins and peptidylarginine deiminases 2 and 4 in neutrophils from rheumatoid arthritis patients.Clinical rheumatology · 2020Article
- Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus.Frontiers in immunology · 2020Article
- Rheumatoid Arthritis-Associated Mechanisms ofJournal of clinical medicine · 2019Review
- Review
- Affinity Maturation of the Anti-Citrullinated Protein Antibody Paratope Drives Epitope Spreading and Polyreactivity in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2019Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveAnti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). However, the molecular basis for ACPA production is still unclear. The purpose of this study was to determine if circulating plasmablasts from RA patients produce ACPAs and whether Porphyromonas gingivalis facilitates the generation of ACPAs.
methodsUsing a single-cell antibody cloning approach, we generated 217 and 110 monoclonal recombinant antibodies from circulating plasmablasts from 7 RA patients and 4 healthy controls, respectively. Antibody reactivity with citrullinated antigens was tested by a second-generation anti-cyclic citrullinated peptide (anti-CCP) kit and by enzyme-linked immunosorbent assays (ELISAs) against citrullinated human antigens. Antibody reactivity with P gingivalis was tested by ELISAs against outer membrane antigens (OMAs) and citrullinated enolase from P gingivalis.
resultsApproximately 19.5% of plasmablast-derived antibodies from anti-CCP-positive RA patients, but none from 1 anti-CCP-negative RA patient or the healthy controls, specifically recognized citrullinated antigens. The immunoglobulin genes encoding these ACPAs were highly mutated, with increased ratios of replacement mutations to silent mutations, suggesting the involvement of active antigen selection in ACPA generation. Interestingly, 63% of the ACPAs cross-reacted with OMAs and/or citrullinated enolase from P gingivalis. The reactivity of ACPAs against citrullinated proteins from P gingivalis was confirmed by immunoblotting and mass spectrometry. Furthermore, some germline-reverted ACPAs retained their reactivity with P gingivalis antigens but completely lost their reactivity with citrullinated human antigens.
conclusionThese results suggest that circulating plasmablasts in RA patients produce ACPAs and that this process may be facilitated by anti-P gingivalis immune responses.
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