Periodontal Disease and Autoimmunity in Rheumatoid Arthritis

Periodontitis is a chronic inflammatory condition driven by microbial dysbiosis of the subgingival biofilm that results in destruction of the supporting structures of the teeth. Rheumatoid arthritis (RA) is an autoimmune disease characterised by synovial inflammation, joint destruction and systemic features that include autoantibodies to citrullinated proteins. Epidemiological and mechanistic studies have identified bidirectional links between these two disorders. Dysbiosis in the oral cavity may trigger systemic inflammation and generate neoepitopes through bacterial or host-derived peptidyl arginine deiminases, resulting in the break of immune tolerance and production of anti-citrullinated protein antibodies. The shared profile of pro-inflammatory cytokines and the enrichment of osteoclastogenic pathways in both gingival and synovial tissues suggest common immunopathogenic pathways that culminate in bone resorption. Conversely, autoimmunity in RA can exacerbate periodontal tissue breakdown, creating a self-perpetuating cycle of inflammation and tissue damage. Understanding these intersections has profound implications for the diagnosis, monitoring and treatment of both diseases.

Research from Nature Portfolio

Foundational work has shown that oral administration of Porphyromonas gingivalis to murine models alters the gut microbiota and compromises intestinal barrier integrity, leading to a T helper 17-driven increase in systemic inflammation and aggravated collagen-induced arthritis. These findings establish a mechanistic link in which a periodontal pathogen can influence distant joint disease by engaging the gut–immune axis and promoting inflammatory osteoclastogenesis.

Periodontal Disease and Autoimmunity in Rheumatoid Arthritis publication trend

The graph below shows the total number of articles in periodontal disease and autoimmunity in rheumatoid arthritis across all publications each year (not limited to Nature Index journals).

Technical terms

Dysbiosis: An imbalance in the composition or function of the microbial community associated with disease.

Citrullination: A post-translational modification of arginine residues to citrulline, altering protein structure and immunogenicity.

Peptidyl arginine deiminase (PAD): An enzyme that catalyses citrullination and can originate from host or bacterial sources, generating neoantigens.

Anti-citrullinated protein antibodies (ACPA): Autoantibodies directed against citrullinated epitopes, highly specific for rheumatoid arthritis.

Osteoclast: A multinucleated cell responsible for bone resorption, which in inflammatory conditions can derive from atypical precursors.

Neutrophil extracellular traps (NETs): Web-like structures composed of DNA and proteins released by neutrophils that can expose autoantigens and promote inflammation.

References

1. Aggravation of collagen-induced arthritis by orally administered Porphyromonas gingivalis through modulation of the gut microbiota and gut immune system. Scientific Reports (2017).
2. New insights into inflammatory osteoclast precursors as therapeutic targets for rheumatoid arthritis and periodontitis. Bone Research (2023).
3. Antibodies against Porphyromonas gingivalis in serum and saliva and their association with rheumatoid arthritis and periodontitis. Data from two rheumatoid arthritis cohorts in Sweden. Frontiers in Immunology (2023).
4. The Effects of Periodontal Treatment on Rheumatoid Arthritis and of Anti-Rheumatic Drugs on Periodontitis: A Systematic Review. International Journal of Molecular Sciences (2023).