Johns Hopkins researchers have linked a specific bacteria involved in gum disease to the processes at hand in rheumatoid arthritis. It may be premature, however, to consider flossing an aspect of joint health.
The notion of a link between gum disease and rheumatoid arthritis (RA) is far from novel. It has been theorized, speculated upon, and studied for decades, with new investigations coming out each year. No matter the confidence that researchers may have held in that link, it was hard to prove without pinpointing the exact mechanism at play.
Researchers from Johns Hopkins believe they may have changed that.
In a study published this week, the team seems to finally draw a line from bacteria in the mouth straight down to the pain felt in the joints of millions of people. Maximilian F. Konig, MD, one of the study’s authors, said the work “may be the closest we’ve come to uncovering the root cause of RA.”
Analyzing periodontal samples, the researchers realized that there was a similar process at play in the gums of patients with periodontal disease as in the joints of people with RA: hypercitrullination. Hypercitrullination is thought to be near the beginning of the cascade chain of RA. When the regular release of citrullinated proteins becomes overactivated, the body produces an extensive amount of antibodies to get rid of them, leading to the immune system’s painful attacks on the body’s own tissue known as RA.
Looking at bacteria associated with periodontal diseases, the team sought to find which ones could initiate this process. Although a variety of bacterial species were detected in hypercitrullinated periodontitis samples, “Aggregatibacter actinomycetemcomitans (Aa), but not other candidate pathogens, induced hypercitrullination in host neutrophils,” the authors wrote.
Identifying the toxin leukotoxin A (LtxA) as the means by which Aa activated this process, boring holes into the surface of neutrophils and causing them to fill with calcium and causing them to overactivate. Having observed a similar toxin involved in the hypercitrullination of joints in RA patients, they theorized in a press release that “a common mechanism that is poking holes on cells” in both gum disease and RA.
Seeking to translate all of this onto a human scale, the researchers searched for antibodies to Aa in blood samples from 196 RA patients. Evidence of Aa infection was present in about 47% of the blood samples, compared with 60% of tested blood samples from patients with periodontal disease. If those numbers seem low, they become significant when compared with healthy controls, in whom only 11% were observed to have evidence of Aa.
While its presence in under half of the RA patients studied leaves open a real possibility that other bacteria elsewhere in the body are responsible for the mechanism, it is the commonality of the specific Aa in both RA and periodontitis patients that excites the researchers. The study acknowledges that the strain is merely a candidate, and that future investigation is always necessary. Still, after decades of looking for a link that so many suspected, this finding brings relief and perhaps some hyperbole.
“This is like putting together the last few pieces of a complicated jigsaw puzzle that has been worked on for many years,” said Felipe Andrade, MD, PhD, the senior investigator, in a corresponding press release.
The study, entitled “Aggregatibacter actinomycetemcomitans—induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis”, was published December 14 in Science Translational Medicine.