This article is more than 5 years old. Information may no longer be current.
Gum Bacterium Linked to Rheumatoid Arthritis
Click Here to Manage Email Alerts
Researchers have identified the gum-dwelling Aggregatibacter actinomycetemcomitans as a potential cause of autoimmunity in patients with a genetic susceptibility to rheumatoid arthritis.
“What we found is when we compare to healthy people, patients with rheumatoid arthritis — about 50% of them — have evidence of infection with this bacterium,” Maximilian F. Konig, MD, clinical fellow in Medicine at Massachusetts General Hospital told Healio Rheumatology. “And compared to healthy people, where maybe 10% of the population have antibodies or evidence of infection, the difference in patients that develop rheumatoid arthritis [RA] seems to be that they have a genetic susceptibility.”
In these patients, Konig and colleagues, including Felipe Andrade, MD, PhD, assistant professor of medicine in the Division of Rheumatology at Johns Hopkins University, hypothesized this bacterium — which secretes pore-forming leukotoxin A (LtxA) — pokes holes in neutrophil cells and leads to an influx of calcium and activation of peptidylarginine deiminase enzyme, which induces hypercitrullination of proteins and causes the immune system to attack its own joint tissue.
Using immunoblotting to detect citrullinated proteins (AMC), the researchers assessed the gingival crevicular fluid (GCF) from 196 patients with RA and 100 healthy controls who did not have periodontitis. To determine microbial and antigenic GCF composition, the researchers used mass spectrometry (MS). After incubation with periodontal pathogens — including Aggregatibacter actinomycetemcomitans (Aa), purified LtxA, P. gingivalis, T. forsythia, T. denticola, F. nucleatum, P. micra, P. intermedia and S. intermedius — the researchers assessed isolated human neutrophils by MS and AMC immunoblotting. The researchers stained the neutrophils — which were incubated alone or with LtxA — with SYTOX Green, anti-citH3 and anti-citrullinated protein antigen-positive RA serum. Using an enzyme-linked immunosorbent assay, they quantified antibodies against Aa and LtxA.
According to a press release from Johns Hopkins Medicine, researchers found 92 of 196 patients with RA and 11% of healthy controls had evidence of Aa. The citrullinome looked similar in periodontitis as it did in the rheumatoid joint. There were several bacterial species in samples of hypercitrullinated periodontitis, but only Aa induced hypercitrullination in host neutrophils, which is also mimicked in RA joints. In addition, LtxA induced changes in neutrophil morphology that mimicked extracellular trap formation. Further, patients exposed to leukotoxic Aa strains were more likely to have anticitrullinated protein antibodies and rheumatoid factor. Only patients with RA who were exposed to Aa showed the effect of human lymphocyte antigen (HLA)-DRB1 shared epitope alleles on auto-antibody positivity, suggesting they have a genetic susceptibility.
These results suggest Aa is a candidate trigger of autoimmunity in RA, the researchers wrote.
“This opens up a whole new possibility of treatment and prevention that usually does not exist,” Konig said. “If this is indeed an agent that can drive the development of this disease, you can think about screening patients who are at high risk of disease, who have this genetic susceptibility, and in those patients, maybe intervene early and try to eradicate this bacterium and stop the disease before it develops.” – by Will Offit
References:
Konig MF, et al. Abstract #913. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington.
Disclosures: Konig reports no relevant financial disclosures. Please see the full study for a list of all other relevant financial disclosures.
Click Here to Manage Email Alerts