Gums & Joints

Rheumatoid arthritis (RA), affecting 0.5-1% worldwide, is a severe systemic autoimmune disease, where patients suffer chronic joint inflammation, causing pain and disability, comorbidities and increased mortality. Inflammation in RA may result from a number of different mechanisms one of the most common being autoantibodies recognizing citrullinated proteins, especially citrullinated enolase, fibrinogen, vitronectin, and collagen. Formation of immune-complexes in joints activates complement, fuels release of proinflammatory cytokines and causes joints' infiltration with immune cells. This leads to synovial edema, fibrin deposition, intensive leukocyte invasion and hyperplasia of the synovial lining cells fueling chronic inflammatory reaction. The final outcome is cartilage damage, bone erosion, and joint destruction. Inflammatory cytokines, especially TNF released locally by leukocytes are driving this destructive cycle.

The specificity and regulation of the underlying autoimmune reactions in RA have for long been elusive, preventing a deeper understanding of disease processes and the development of a cure. However, the discovery of antibodies reactive with citrullinated proteins has given us an opportunity, and a biological tool, to improve this situation. These antibodies, present in approximately 70% of patients, are (i) disease-specific; (ii) associate with major susceptibility factors (most notably specific HLA-DRB1 alleles and cigarette smoking); (iii) associate with a more severe disease course, suggesting a pathogenic involvement; and (iv) are present before clinical onset, which may indicate that the initial loss of immune tolerance to citrullinated proteins occur as a consequence of an inflammatory event outside the joint. Furthermore, the presence of IgA anti-citrullinated protein antibodies may point towards the involvement of mucosal surfaces, such as the gingiva.

Clinical link between periodontitis and rheumatoid arthritis

RA is fueled by disease-specific autoantibodies to citrullinated proteins, products of physiological post-translational modification of proteins by endogenous peptidylarginine deiminases (PADs). Factors which trigger the breakdown of tolerance to citrullinated proteins are unknown. Interestingly, clinical studies of RA and periodontitis have provided strong evidence for a significant association between the two diseases. Patients with long- standing, active RA have a substantially increased frequency of periodontitis as compared with healthy subjects. Vice versa, patients with periodontal disease have higher prevalence of RA than patients without periodontitis. The expression of PAD by P. gingivalis (unique for this bacterium) may constitute a mechanistic link explaining the clinical correlation between RA and periodontitis. Protein citrullinationby P. gingivalis may expose new protein epitopes. In the context of a bacteria-driven inflammatory response, the presence of endogenous and exogenous danger signals may trigger a latent antibody response to citrullinated bacterial and self-proteins and hence, initiate an autoimmune destructive reaction.