Researchers identify oral bacterium that could be a key to understanding RA

periodontitis and bleedingResearchers have observed an association between rheumatoid arthritis and gum disease since the early 1900s, and over time they’ve suspected that a common factor might trigger both. But a good understanding of how they relate remains evasive, says Felipe Andrade, an associate professor of medicine (rheumatology) at Johns Hopkins University School of Medicine.

“The tantalizing association between gum disease and RA sparked our interest in understanding how these diseases may be related,” says Dr. Andrade, who with colleagues published a study late last year in Science Translational Medicine. The study identified Aggregatibacter actinomycetemcomitans (Aa), a kind of oral bacteria, as a common denominator that could explain the association between RA and periodontal (gum) disease.

“We found that among many bacteria associated with periodontal disease, Aa has the unique capacity of inducing hypercitrullination, which is suspected of activating the immune system and driving the cascade of events leading to RA,” he says.

Writing about Dr. Andrade and colleagues’ research recently in the Journal of the American Medical Association, Jennifer Abbasi notes how surprising the study will be to many people. “The mouth may seem like a strange place to search for a culprit in a disease that primarily affects the joints,” she writes.

Specifically, the study found the following:

  1. Nearly half of patients with RA in the study had evidence of Aa infection, compared to just 11 percent of healthy individuals, who didn’t have RA.
  2. In patients genetically susceptible to RA, exposure to the bacterium Aa was an important factor in the production of antibodies to citrullinated proteins.

The process of citrullination occurs naturally in every person, in order to regulate protein function, but in those with RA, it becomes overactive, which results in hypercitrullination, Dr. Andrade explains. That leads to abnormal amassing of citrullinated proteins, which drives production of antibodies against those proteins. The antibodies create inflammation and attack joints in RA patients.

The new research is exciting, but Dr. Andrade cautions against overstating what it means.

“Patients must be aware that our research cannot yet be applied to novel diagnostic tests or to make changes in the current therapies for patients with RA,” he says. “Nevertheless, regardless of these limitations, patients should know about the strong association between gum disease and rheumatoid arthritis.”

He and his co-authors, as well colleagues elsewhere, are trying to identify better ways to treat — and potentially cure — RA patients, and they’re doing that by studying gum diseases. His group’s findings await independent validation, he says, and direct demonstration is needed that the kind of bacterium can induce RA in experimental models.

“About 50 percent of the study participants who had RA had no evidence of infection with Aa, which may indicate that other bacteria in the gut, lung, or elsewhere could be using a similar mechanism to induce hypercitrullination,” he says. “Identifying such bacteria is part of the next plan for the future.”

Clinical studies will also play a vital role in guiding the translation and understanding of the findings to bedsides, and to determining whether the data can be used to improve treatment strategies or to help at-risk patients from a preventative perspective.

“Patients should be evaluated and seek treatment if they have periodontal disease,” Dr. Andrade says. “Importantly, gum disease is not only associated with RA, but has been linked to other chronic diseases. Healthy individuals should be aware that having an appropriate oral hygiene is not only about the aesthetic of the mouth, but might be relevant to prevent serious diseases such as RA.”