Journal ArticleDOI
Hypothesis: The Humoral Immune Response to Oral Bacteria Provides a Stimulus for the Development of Rheumatoid Arthritis
TLDR
It is suggested that individuals predisposed to periodontal infection are exposed to antigens generated by PAD, with deiminated fibrin as a likely candidate, which become systemic immunogens and lead to intraarticular inflammation.Abstract:
Rheumatoid arthritis (RA) and adult periodontitis share common pathogenetic mechanisms and immunologic and pathological findings. One oral pathogen strongly implicated in the pathogenesis of periodontal disease, Porphyromonas gingivalis, possesses a unique microbial enzyme, peptidylarginine deiminase (PAD), the human equivalent of which has been identified as a susceptibility factor for RA. We suggest that individuals predisposed to periodontal infection are exposed to antigens generated by PAD, with deiminated fibrin as a likely candidate, which become systemic immunogens and lead to intraarticular inflammation. PAD engendered antigens lead to production of rheumatoid factor-containing immune complexes and provoke local inflammation, both in gingiva and synovium via Fc and C5a receptors.read more
Citations
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Journal ArticleDOI
Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis
Natalia Wegner,Karin Lundberg,Andrew J Kinloch,Benjamin A Fisher,Vivianne Malmström,Marc Feldmann,Patrick J Venables +6 more
TL;DR: Rheumatoid arthritis (RA) is now clearly a true autoimmune disease with accumulating evidence of pathogenic disease‐specific autoimmunity to citrullinated proteins, and both smoking and Porphyromonas gingivalis are attractive etiological agents for further investigation into the gene/environment/autoimmunities triad of RA.
Journal ArticleDOI
Periodontitis in systemic rheumatic diseases.
TL;DR: There is evidence to suggest that periodontitis could indeed be a causal factor in the initiation and maintenance of the autoimmune inflammatory response that occurs in RA.
Journal ArticleDOI
Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase.
Karin Lundberg,Andrew J Kinloch,Benjamin A Fisher,Natalia Wegner,Robin Wait,Peter Charles,Ted R. Mikuls,Patrick J Venables +7 more
TL;DR: The data on sequence similarity and cross-reactivity with bacterial enolase may indicate a role for bacterial infection, particularly with P gingivalis, in priming autoimmunity in a subset of patients with RA.
Journal ArticleDOI
Periodontal inflamed surface area: quantifying inflammatory burden
Willem Nesse,Frank Abbas,Ids van der Ploeg,F.K.L. Spijkervet,Pieter U. Dijkstra,Arjan Vissink +5 more
TL;DR: PISA quantifies the inflammatory burden posed by periodontitis and can be easily and broadly applied.
Journal ArticleDOI
Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis.
Ted R. Mikuls,Jeffrey B. Payne,Fang Yu,Geoffrey M. Thiele,Richard J. Reynolds,Grant W. Cannon,Jeffrey Markt,David McGowan,Gail S. Kerr,Robert S. Redman,Andreas M. Reimold,Garth R. Griffiths,Mark W. Beatty,Shawneen M. Gonzalez,Debra A. Bergman,Bartlett C. Hamilton,Alan R Erickson,Jeremy Sokolove,William H. Robinson,Clay Walker,Fatiha Chandad,James R. O'Dell +21 more
TL;DR: To examine the degree to which shared risk factors explain the relationship of periodontitis to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.
References
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Journal ArticleDOI
Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors
Elizabeth A. Leadbetter,Ian R. Rifkin,Andreas Hohlbaum,Britte C. Beaudette,Mark J. Shlomchik,Ann Marshak-Rothstein +5 more
TL;DR: It is shown that effective activation of RF+ B cells is mediated by IgG2a–chromatin immune complexes and requires the synergistic engagement of the antigen receptor and a member of the MyD88-dependent Toll-like receptor (TLR) family.
Journal ArticleDOI
Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis.
Solbritt Rantapää-Dahlqvist,Ben A. W. de Jong,Ewa Berglin,Göran Hallmans,Göran Wadell,Hans Stenlund,Ulf Sundin,Walther J. van Venrooij +7 more
TL;DR: Anti-CCP antibody and RFs of all isotypes predated the onset of RA by several years, indicating that citrullination and the production of anti- CCP and RF autoantibodies are early processes in RA.
Journal ArticleDOI
Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.
G.A. Schellekens,B.A. de Jong,F.H.J. van den Hoogen,L. B. A. Van De Putte,W. J. Van Venrooij +4 more
TL;DR: It is shown that autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue, are specifically present in the sera of RA patients, and the presence of these antibodies early in disease, even before other disease manifestations occur, are indicative for a possible role of citrulling epitopes in the pathogenesis of RA.
Journal ArticleDOI
Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis.
Akari Suzuki,Ryo Yamada,Xiaotian Chang,Shinya Tokuhiro,Tetsuji Sawada,Masakatsu Suzuki,Miyuki Nagasaki,Makiko Nakayama-Hamada,Reimi Kawaida,Mitsuru Ono,Masahiko Ohtsuki,Hidehiko Furukawa,Shinichi Yoshino,Masao Yukioka,Shigeto Tohma,Tsukasa Matsubara,Shigeyuki Wakitani,Ryota Teshima,Yuichi Nishioka,Akihiro Sekine,Aritoshi Iida,Atsushi Takahashi,Tatsuhiko Tsunoda,Yusuke Nakamura,Kazuhiko Yamamoto +24 more
TL;DR: The results imply that the PADI4 haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease.
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The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
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