Bacterium That Causes Gum Disease May Trigger Rheumatoid Arthritis

Study findings may improve the prevention and treatment of rheumatoid arthritis.

Investigators have identified a common denominator in periodontal disease and rheumatoid arthritis (RA), called hypercitrullination, which may play a role in the development of RA.

Citrullination occurs naturally in humans as a way to regulate the function of proteins, but for patients with RA, the process becomes overactive and results in abnormal accumulation of citrullinated proteins. This abnormality drives the production of antibodies against proteins that create inflammation, and attack the body’s own tissues.

The investigators examined different bacteria associated with periodontal disease, and found that Aggregatibacter actinomycetemcomitans was the only pathogen that could induce hypercitrullination in neutrophils.

The authors noted that neutrophils have been studied for years as a major source of hypercitrullination in RA. The latest findings were published in Science Translational Medicine.

A. actinomycetemcomitans initiates hypercitrullination through the bacterial secretion of the toxin, leukotoxin A (LtxA), as a strategy to kill host immune cells, according to the study.

LtxA forms holes on the surface of neutrophils, which allows high amounts of calcium to enter into the cell where the concentrations are normally low. Since the peptidylarginine deminase enzymes are activated with calcium, this abrupt exposure to high amounts of calcium causes the enzymes to become overactivated, producing hypercitrullination.

The investigators developed a test that used the bacterium and LtxA to detect antibodies against A. actinomycetemcomitans in the blood of 196 samples from a large study of patients with RA.

The results of the study showed that 92 out of 196 patients had evidence of infection by A. actinomycetemcomitans, which was similar to patients with periodontal disease with approximately 60% positivity. However, the data differed from healthy controls, who had 11% of people positive for A. actinomycetemcomitans.

Most notably, exposure to A. actinomycetemcomitans was a major determinant in the production of antibodies to citrullinated proteins in patients with genetic susceptibility to RA, according to the study.

“This is like putting together the last few pieces of a complicated jigsaw puzzle that has been worked on for many years,” said senior investigator Felipe Andrade, MD, PhD.

The investigators warned that more than 50% of participants with RA had no evidence of infection with A. actinomycetemcomitans. This suggests that other bacteria in the lung, gut, or elsewhere, could be using a similar mechanism to induce hypercitrullination.

A limitation to the study was that investigators only examined patients at a single point in time with established RA. In order to prove cause and effect of A. actinomycetemcomitans and RA, more research needs to be done to track the potential role of the bacteria in the onset and evolution on the disease.

“If we know more about the evolution of both combined, perhaps we could prevent rather than just intervene,” Andrade said.