A bacterium that causes gum infections may also contribute to inflammation leading to chronic joint-destroying rheumatoid arthritis (RA), according to new research. This could provide useful information on how to prevent and treat RA.
The fact that gum infection and RA are associated is not new, but for years researchers have struggled to find the common factor linking these conditions. Johns Hopkins researchers now say the bacterium Aggregatibacter actinomycetemcomitans appears to be the common link.
Their study, “Aggregatibacter actinomycetemcomitans–Induced Hypercitrullination Links Periodontal Infection To Autoimmunity In Rheumatoid Arthritis,” was published in the journal Science Translational Medicine.
“This is like putting together the last few pieces of a complicated jigsaw puzzle that has been worked on for many years,” Felipe Andrade, MD, PhD, the senior author of the study, said in a news release.
“This research may be the closest we’ve come to uncovering the root cause of RA,” added Maximilian Konig, MD, the first author of the study.
Previous studies have suggested it could be the bacterium Porphyromonas gingivalis, which is present in patients with gum disease, but evidence linking this infection with RA is still lacking.
The research team led by Andrade found that gum disease manifests through a process that had also been observed in the joints of RA patients, called hypercitrullination.
According to Andrade, citrullination is a natural process in the body that regulates the function of proteins. In RA patients, however, this process becomes overactive, causing an abnormal increase in citrullinated proteins. The body then reacts to the presence of these proteins, causing inflammation and attacking the person’s own tissue.
The researchers observed that infection by A. actinomycetemcomitans could trigger hypercitrullination in neutrophils, a type of immune cell enriched in proteins that participate in the citrullination process. According to the researchers, neutrophils can be found in increased levels in the joints and gums of patients with RA and gum disease.
The bacterium promotes hypercitrullination by producing a bacterial molecule to protect themselves and kill immune system cells, called leukotoxin A (LtxA). This molecule opens holes in neutrophils, allowing high levels of calcium to enter the cells. Because citrullination is activated by calcium, an increase in calcium levels triggers hypercitrullination in neutrophils.
As this process has been found to occur in the joints of RA patients as well, it may be that A. actinomycetemcomitans is indeed the common triggering factor for both RA and gum disease.
Researchers developed a test that allowed them to detect levels of antibodies against the bacterium in the blood. They tested it in 196 RA patients and observed that nearly half of this group (92 patients) was infected by A. actinomycetemcomitans. Similarly, they found that 60 percent of patients with gum disease were also infected with these bacteria.
According to Andrade, the fact that more than half of the RA patients had no signs of A. actinomycetemcomitans infection suggests that other bacteria may induce hypercitrullination.
The team believes that more studies are warranted to determine whether A. actinomycetemcomitans has indeed a cause-and-effect role in RA.
