Link found between periodontal disease and rheumatoid arthritis

Link found between perio disease and rheumatoid arthritis

Investigators at Johns Hopkins University, Baltimore, Maryland, report they have new evidence that a bacterium known to cause chronic inflammatory periodontal infections also triggers the inflammatory autoimmune response characteristic of chronic, joint-destroying rheumatoid arthritis. The new findings have important implications for prevention and treatment of this condition, say the researchers.

In a report on the work, published in the journal Science Translational Medicine, the investigators say the common denominator they identified in periodontal disease and in many people with rheumatoid arthritis is Aggregatibacter actinomycetemcomitans. An infection with A. actinomycetemcomitans appears to induce the production of citrullinated proteins, which are suspected of activating the immune system and driving the cascade of events leading to rheumatoid arthritis.

"This is like putting together the last few pieces of a complicated jigsaw puzzle that has been worked on for many years," says Dr Felipe Andrade, the senior study investigator and associate professor of Medicine at the Johns Hopkins University School of Medicine. "This research may be the closest we've come to uncovering the root cause of rheumatoid arthritis," adds first author Maximilian Konig, M.D., a former Johns Hopkins University School of Medicine fellow now at Massachusetts General Hospital.

Medical investigators have observed a clinical association between periodontal disease and rheumatoid arthritis since the early 1900s, and over time, researchers have suspected that both diseases may be triggered by a common factor. In the last decade, studies have focused on a bacterium known as Porphyromonas gingivalis, found in patients with gum disease. However, while major efforts are currently ongoing to demonstrate that this bacterium causes rheumatoid arthritis by inducing citrullinated proteins, all attempts by this research team have failed to corroborate such a link, says Andrade. But his team has persisted on finding alternative bacterial drivers, he says, because of intriguing links between periodontal disease rheumatoid arthritis.

For this study, the investigative team with expertise in periodontal microbiology, periodontal disease and rheumatoid arthritis began to search for a common denominator that may link both diseases. Initial clues came from the study's analysis of periodontal samples, where they found that a similar process that had previously been observed in the joints of patients with rheumatoid arthritis was occurring in the gums of patients with periodontal disease. This common denominator is called hypercitrullination.

Andrade explains that citrullination happens naturally in everyone as a way to regulate the function of proteins. But in people with RA, this process becomes overactive, resulting in the abnormal accumulation of citrullinated proteins. This drives the production of antibodies against these proteins that create inflammation and attack a person's own tissues, the hallmark of rheumatoid arthritis.

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