“In periodontitis, the gingival crevicular fluid becomes inflamed with polymorphonuclear leukocytes (PMNs) and matrix metalloproteinases (MMPs), and this favors certain anaerobic organisms that are able to flourish in an inflammatory environment,” he said. One particularly high-risk pathogen, Aggregatibacter actinomycetemcomitans (Aa), may cause severe periodontitis. Porphyrmonas gingivalis is another risky pathogen associated with gum disease. Research published in 2016 reveals that gingival crevicular fluid (GCF) showed extensive citrullination, mirroring the pattern of hypercitrullination of proteins seen in RA joints.6 Only P. gingivalis has a petidylarginine deiminase (PAD) enzyme that citrullinates arginines at the C-terminal portions of the protein, which may lead to immunoreactive neoepitopes, he said.7
However, the study’s authors “found that RA patients have citrullines in the middle portion of their proteins, as one would expect from citrullination caused by host PADs, not at the C-terminal ends, as with P. gingivalis PADs. They further showed that Aggregatibacter has a leukotoxin, which causes intracellular release of PADs from polymorphonuclear leukocytes. And only Aggregatibacter had the ability to produce a similar repertoire of citrullinated antigens in the GCF as in the RA joint.” It is important to learn whether such processes can play out in the gut, he said.
P. copri & RA
Other bacteria play a role in RA, especially P. copri. A 2013 study found overexpansion of Prevotella bacteria, especially P. copri, in the stool samples of 75% of patients with new-onset RA compared to a significantly smaller percentage of patients with chronic RA or healthy controls.8 P. copri expansion was at the expense of other species, such as Bacteroides, and particularly B. fragilis, which may be important in T-regulatory cell development and function, said Dr. Steere.