How periodontal disease contributes to inflammation and rheumatoid arthritis

Periodontal diseases enable oral mucosa tears, where citrullinated bacteria enter the bloodstream, leading to inflammatory immune cells and ACPA antibodies.

Injuries to the oral mucosa trigger anti-citrulline antibodies (ACPA) against bacteria and human proteins

Is inflammation of the oral mucosa involved in the development of RA?

Periodontal diseases often cause micro-injuries in the oral mucosa, which become entry points for oral germs into the blood. The importance of citrullinated bacteria as a possible infectious trigger for autoimmunity has been discussed for some time. It is assumed that certain bacterial strains, such as Porphyromonas gingivalis, mediate the citrullination of host proteins and thus the formation of RA-associated autoantibodies in genetically predisposed individuals.2

The realisation that many RA autoantibodies are directed against citrulline in peptides was a significant breakthrough shortly before the turn of the millennium, and has since been used diagnostically as a sensitive biomarker, as many of these peptides are specific for RA and ACPA antibodies (antibodies against citrullinated proteins) can already be detected in the early stages of the disease. Citrullination of specific connective tissue proteins (such as filaggrin, vimentin, fibrin, fibrinogen, α-enolase and collagen II) generates new epitopes that lead to the formation of autoantibodies.3

Growing evidence for a direct link between periodontal disease and rheumatoid arthritis

A 2019 UK study was one of the first to conclude that periodontal inflammation and the accumulation of P. gingivalis may precede joint inflammation in RA.4 The new data also supports a link between these risk factors and the onset of the disease. The Stanford team was able to show that patients with RA and periodontal disease experience repeated oral bacteraemia.

These were associated with transcriptional signatures of inflammatory monocytes recently identified in inflamed RA synovium and in the blood of RA patients during relapses.1 In response to the oral bacteria entering the blood, ACPA-specific B cells were also activated, promoting affinity maturation and epitope spreading to citrullinated human antigens.1

Gum disease could be involved in the flare-up of arthritis

The prevalence of periodontitis is increased in patients with rheumatoid arthritis and periodontopathic bacteria can citrullinate proteins. Periodontitis could therefore be a trigger for RA and a target for prevention.4 Analogous findings have already been well documented for cardiovascular disease: People with periodontal disease have a two to three times higher risk of myocardial infarction, stroke, or other serious cardiovascular events.5 More attention should therefore be paid to improving oral health (for example, by reducing sugar and starch consumption, to name just one issue).

  1. Brewer, R. C. et al. Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis. Science Translational Medicine 15, eabq8476 (2023).
  2. Reichert, S. et al. Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study. Journal of Translational Medicine 13, 283 (2015).
  3. Citrullination and Autoimmunity. Biomol GmbH - Life Science Shop
  4. Mankia, K. et al. Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti–Cyclic Citrullinated Protein Antibody–Positive At-Risk Adults Without Arthritis. JAMA Network Open 2, e195394 (2019).
  5. Gum disease and heart disease: The common thread. Harvard Health (2018).