By Pat Anson, Editor
Scientists have long suspected that pathogens and bacterial infections may play a role in the development of autoimmune diseases such as rheumatoid arthritis (RA). Now there is evidence that a bacterium associated with chronic gum infections may trigger an inflammatory response characteristic of RA, a discovery that could lead to new ways to treat and prevent the disease.
"This research may be the closest we've come to uncovering the root cause of RA," said Maximilian Konig, MD, a former Johns Hopkins University School of Medicine fellow now at Massachusetts General Hospital.
Rheumatoid arthritis is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. About 1.5 million Americans and one percent of adults worldwide suffer from RA. There is no cure for the disease and treatments only focus on slowing its progression.
In a study of nearly 200 RA patients, Konig and his colleagues found that nearly half had antibodies against Aggregatibacter actinomycetemcomitans in their blood.
The level of infection with the bacteria was similar in patients with periodontal (gum) disease, but quite different in healthy patients, only 11 percent of whom tested positive for A. actinomycetemcomitans.
An infection with A. actinomycetemcomitans appears to induce the production of citrullinated proteins, which are suspected of activating the immune system and driving the cascade of events leading to RA.
"This is like putting together the last few pieces of a complicated jigsaw puzzle that has been worked on for many years," says Felipe Andrade, MD, a senior study investigator and associate professor of Medicine at the Johns Hopkins University School of Medicine.
Andrade cautions that over half of the study participants with RA had no evidence of an infection with A. actinomycetemcomitans, which may indicate that other bacteria in the gut, lung or elsewhere could be involved. He says more research is needed to determine if there is a cause and effect relationship between bacteria and RA.
"If we know more about the evolution of both combined, perhaps we could prevent rather than just intervene," he said.
The Johns Hopkins study is published in the journal Science Translational Medicine.
Scientists have observed an association between periodontal disease and RA since the early 1900s, and have suspected that both diseases may be triggered by a common factor. In the last decade, studies have focused on a bacterium known as Porphyromonas gingivalis, which is found in patients with gum disease. However, research has so far failed to corroborate such a link.
Researchers in the current study found inflammation in the joints of RA patients that was similar to the inflamed gums of patients with periodontal disease, an inflammatory process known as hyper-citrullination.
Citrullination occurs naturally in everyone as a way to regulate the function of proteins. But in people with RA, the process becomes hyperactive, resulting in the abnormal accumulation of citrullinated proteins. This drives the production of antibodies against proteins that create inflammation and attack a person's own tissues, the hallmark of RA.