Periodontitis and arthritis

IS PERIODONTAL DISEASE A COMORBIDITY…? Relationship Between Periodontal Disease and Rheumatoid Arthritis

The disease involves inflammation of the joints, with cartilage degradation and joint deformity, swelling, and pain. PD and RA may associate bidirectionally. Both diseases display elevated circulating and target tissue levels of markers of inflammation and cytokine profiles of ‘tissue degrading’ nature, including increased production of IL-1 and tumor necrosis factor alpha (TNF-α). RA is furthermore characterized by the formation of autoantibodies, including rheumatoid factors recognizing immunoglobulin G (IgG) and antibodies to citrullinated proteins (ACPAs). The latter are found in approximately three-quarters of RA patients, which also have a characteristic expression of major histocompability complex molecules capable of binding citrullinated peptides. Post-translational conversion of the amino acid arginine to citrulline is catalyzed by enzymes of the peptidylarginine deiminase (PAD) family, and these are considered important in disease progression, at least in ACPA-positive RA.

Patients with antibodies against citrullinated proteins more frequently appear to have PD than patients with osteoarthritis do. In addition, RA patients more frequently have antibodies against Porphyromonas gingivalis than healthy controls do. P. gingivalis, which is the only bacterium with capacity to produce a PAD (PPAD). Like the corresponding human enzyme, PPAD is capable of converting arginine to citrulline. In theory, PPAD may therefore convert harmless host proteins into citrullinated autoantigens that become the target for autoantibodies and pathogenic T- cells that drive RA. Smoking, which increases the risk of PD, is also the strongest life-style factor linked to the development of RA. Smoking is also believed to promote the secretion of PAD from leukocytes in the lungs and thus initiate citrullination. The available studies, however, are small and with limited follow-up, but they suggest that non-surgical periodontal treatment may reduce clinical symptoms and biomarkers of active RA.

Most studies have measured several RA-specific and ancillary pro-inflammatory biomarkers (e.g. RF, ACP; and TNF-α, IL-1β etc., respectively). Although identification of candidate biomarkers is an important objective, these markers were highly variable both at baseline and after treatment and did not appear to be suitable as independent measures of disease activity. Although levels of inflammatory markers offer one explanation for a common mechanism of action for the impact of periodontal therapy on both periodontal disease and RA activity, most of these biomarkers do not appear to be useful proxies for more robust clinical measures, such as DAS-28 for RA or bleeding on probing/probing pocket depth for periodontal disease. One promising biomarker as an outcome measure for assessing the impact of NSPT on RA disease activity is ACPA, for which three studies found there to be a significant reduction after treatment