The case for periodontitis in the pathogenesis of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA), an autoimmune disease that affects ∼1% of the human population, is driven by autoantibodies that target modified self-epitopes, whereas ∼11% of the global adult population are affected by severe chronic periodontitis, a disease in which the commensal microflora on the tooth surface is replaced by a dysbiotic consortium of bacteria that promote the chronic inflammatory destruction of periodontal tissue. Despite differences in aetiology, RA and periodontitis are similar in terms of pathogenesis; both diseases involve chronic inflammation fuelled by pro-inflammatory cytokines, connective tissue breakdown and bone erosion. The two diseases also share risk factors such as smoking and ageing, and have strong epidemiological, serological and clinical associations. In light of the ground-breaking discovery that Porphyromonas gingivalis, a pivotal periodontal pathogen, is the only human pathogen known to express peptidylarginine deiminase, an enzyme that generates citrullinated epitopes that are recognized by anti-citrullinated protein antibodies, a new paradigm is emerging. In this Review, the clinical and experimental evidence supporting this paradigm is discussed and the potential mechanisms involved in linking periodontitis to RA are presented.

Periodontal status among elderly inhabitants of northern Manhattan: The WHICAP ancillary study of oral health

“…Interestingly, arthritis emerged as significantly and negatively associated with tooth retention. Although our analyses did not precisely differentiate between different forms of arthritic disease, and arthritis was not significantly associated with periodontal status in any model, recent literature suggests a reciprocal association between rheumatoid arthritis and periodontitis (Fuggle et al, 2016, Potempa et al., 2017). …”

Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease

“…Thus, P. gingivalis is a typical example of a pathogen that shows this trait by adapting to challenging inflammophilic environments of the host directed to kill it [8]. The virulence and potential pathogenic effects of P. gingivalis are diverse and, through them, this bacterium can affect many different organs and diseases [3,6,7,9,10]. The virulence factor under focus here is the enzyme P. gingivalis peptidyl-arginine deiminase (PPAD).…”

“…This enzyme modifies both bacterial and host proteins by deimination of arginine residues in proteins and peptides, converting them to citrulline [11–13] (Figure 2). Protein citrullination causes deregulation of the host’s inflammatory signalling network by altering the spatial arrangement of the original 3D-structure and function of the protein [3,6]. This may lead to exposure of damage- and/or pathogen associated molecular patterns (PAMP/DAMP) which can then be used by pattern recognition receptors (PRR), to provide entry and immune evasion [14].…”

“…Subsequent immune responses directed against the bacterial antigens by the infected organ can lead to tissue damage. In some individuals, this can initiate autoimmune responses [3,6] (Figure 3). At present, P. gingivalis is the only known pathogen that produces PPAD [3].…”

Type IX secretion system : characterization of an effector protein and an insight into the role of c-terminal domain dimeration in outer membrane translocation.

“…Later, this can progress into an advanced inflammatory condition called periodontitis leading to the destruction of connective tissue attachment, alveolar bone resorption and eventually tooth loss [6,7]. Periodontitis has also been linked with several systemic diseases like respiratory infections [8], esophageal cancer [9], cardiovascular diseases [10], gestational diabetes [11], and rheumatoid arthritis [12].…”