NEW YORK — A single enzyme, peptidylarginine deiminase, may trigger the autoimmune process that results in rheumatoid arthritis among some people with periodontitis, Dr. Gerald Weissmann said at a rheumatology meeting sponsored by New York University.
Researchers established the association between rheumatoid arthritis and periodontal disease a decade ago (Eur. J. Med. Res. 1998;3:387–92). The same investigators went on to confirm the link, and found that the severity of RA based on a variety of markers—such as swollen joint counts, health assessment questionnaire scores, levels of C-reactive protein, and erythrocyte sedimentation rates—was directly related to the extent of periodontal bone loss in these patients (J. Periodontol. 2001;72:779–87).
The metabolic link that associates the two disorders appears to be a specific family of citrullinated proteins. These proteins have been suggested to act as an auto-antigen in RA, and autoantibodies to these proteins (anti-CCP) are highly specific for RA, according to Dr. Weissmann.
Proteins become citrullinated by the enzyme peptidylarginine deiminase, which is secreted by neutrophils, macrophages, and endothelium. Interestingly, only one bacterium, the oral pathogen Porphyromonas gingivalis the major cause of periodontal disease, produces this enzyme.
One of these citrullinated proteins (deiminated fibrin) may become a systemic immunogen in people who are predisposed to periodontal disease, leading to both periodontal and intra-articular inflammation. The ensuing events—involving the cascade of complement activation, phagocyte stimulation via Fc and C5a receptors, and the release of cytokines, metalloproteinases, and reactive oxygen species—ultimately result in the erosion of bone surrounding teeth and joints.
As further evidence of the link, anti-CCP titers are more predictive of joint damage at 5 years than are rheumatoid factor (RF) titers. Depletion of B cells by rituximab also lowers anti-CCP titers, and to a greater extent than it reduces RF titers (Arthritis Res. 2000;2:249–51), said Dr. Weissmann, research professor of medicine and director of the biotechnology study center at New York University.
Dr. Weissmann traced the rise of rheumatoid diseases in both England and the American colonies to the increased affordability of sugar in the late 18th and early 19th centuries. Before 1773, it was unlikely that working-class residents of the American colonies or London either had access to sugar or developed rheumatoid diseases. Access to sugar became the norm and rheumatoid arthritis became widespread only after the sugar tax was abolished in 1874, he said.
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