Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis.
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 de-iminated 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.
Rosenstein
Elliot D
ED
Center for Rheumatic and Autoimmune Diseases, Livingston, New Jersey 07039, USA. Erostein@sbhcs.com
Greenwald
Robert A
RA
Kushner
Laura J
LJ
Weissmann
Gerald
G
D000328:Adult; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004198:Disease Susceptibility / Q000209:etiology / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D006867:Hydrolases / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D009061:Mouth Mucosa / Q000382:microbiology*; D010518:Periodontitis / Q000209:etiology / Q000382:microbiology / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000201:enzymology* / Q000472:pathogenicity; D000076342:Protein-Arginine Deiminases; D012217:Rheumatoid Factor / Q000096:biosynthesis / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology
D012217:Rheumatoid Factor; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases