Rheumatoid arthritis: strong evidence of links to periodontal disease bacterium, A. actinomycetemcomitans

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Takeaway
  • A bacterium implicated in periodontal disease, Aggregatibacter actinomycetemcomitans, also may initiate rheumatoid arthritis (RA) via hypercitrullination in host neutrophils.
Why this matters
  • The mechanisms linking periodontal disease to RA are an area of strong research interest with significant clinical implications.
Study design
  • Serum from 196 patients with RA who were assessed for disease activity and severity at baseline and at follow-up visit with the last average more than 3 y after baseline.
  • Sera were also obtained from 109 patients with chronic periodontitis and 100 healthy control patients without periodontitis, with mass spectrometry to identify microbial make-up and antigens in fluid collected from the space between the gingival mucosa and tooth.
Key results
  • Levels of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum ssp, Prevotella intermedia, and A actinomycetemcomitans were elevated in hypercitrullinated periodontitis samples.
  • Of these species, only A actinomycetemcomitans upon neutrophil stimulation reproduced patterns of cellular hypercitrullination seen in the gingival crevicular fluid samples of patients with periodontitis and synovial fluid of patients with RA.
  • A actinomycetemcomitans produces a leukotoxin that appears to cause dysregulation of the activation of citrullinating enzymes in neutrophils.
Limitations
  • No evidence that A actinomycetemcomitans triggers production of autoantibodies against citrullinated proteins in vivo.