Hypothesis: The Humoral Immune Response to Oral Bacteria Provides a Stimulus for the Development of Rheumatoid Arthritis
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Hypothesis: The Humoral Immune Response to Oral Bacteria Provides a Stimulus for the Development of Rheumatoid Arthritis Elliot D. Rosenstein,1,4 Robert A. Greenwald,2 Laura J. Kushner,1 and Gerald Weissmann3
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. KEY WORDS: rheumatoid arthritis; periodontitis; Porphyromonas gingivalis; peptidylarginine deiminase; citrulline.
Adult periodontitis (AP) has recently been linked to a variety of systemic medical disorders, including coronary artery disease, stroke, osteoporosis, and low birth weight. (1–2) However, these associations are based almost entirely on epidemiologic data. Although some shared and potentially pathogenic associations, such as levels of C-reactive protein, have been identified, in most cases there is no obvious common disease mechanism (3). On the other hand, adult periodontitis and rheumatoid arthritis (RA) are remarkably parallel disease processes that share not only some clinical features, but pathophysiologic, epidemiological, and therapeutic features as well.
Rheumatoid Arthritis and Periodontitis: Common Pathophysiologic Mechanisms In 1982, Snyderman and McCarty first commented on inflammatory mechanisms common both to rheumatoid arthritis and adult periodontitis. Both RA and AP are characterized by self-sustaining inflammation in a fluidfilled compartment adjacent to bone, in which inflammatory cells and other phlogistic factors lead to common clinical manifestations (pain, swelling, tenderness) and, eventually, to erosion of the adjacent bone (4). Patients with active RA demonstrate significantly increased frequency and severity of periodontal disease, particularly more gingival bleeding and calculus formation, as well as more tooth loss and decreased alveolar bone height as compared to unaffected controls (5–6). In a recent pilot study, it was reported that subjects with AP had a fourfold increased incidence of RA, although the study was seriously flawed by the use of a self-reported diagnosis of RA (7). In a subsequent study, this same group performed careful dental exams on 65 subjects with validated RA and matched controls. They found that the RA patients had more missing teeth and deeper gingival
1 Center
for Rheumatic and Autoimmune Diseases, Livingston, New Jersey. 2 Division of Rheumatol
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