Researchers at the University of Colorado School of Medicine have found {that a} distinctive bacteria discovered in the gut may very well be accountable for triggering rheumatoid arthritis (RA) in folks already at risk for the autoimmune disease.
Kristine Kuhn, MD, PhD, affiliate professor of rheumatology, led a group of researchers from the Division of Rheumatology on the research, which printed on October 26 in the journal Science Translational Medicine. CU School of Medicine scholar Meagan Chriswell is the lead writer of the paper.
“Work led by co-authors Drs. Kevin Deane, Kristen Demoruelle, and Mike Holers here at CU helped establish that we can identify people who are at risk for RA based on serologic markers, and that these markers can be present in the blood for many years before diagnosis,” Kuhn says. “When they looked at those antibodies, one is the normal class of antibody we normally see in circulation, but the other is an antibody that we usually associate with our mucosa, whether it be the oral mucosa, the gut mucosa, or the lung mucosa. We started to wonder, ‘Could there be something at a mucosal barrier site that could be driving RA?'”
Discovering a brand new bacterium
The CU researchers, with the assist of a gaggle led by Bill Robinson, MD, PhD, at Stanford University, took the antibodies created by immune cells from people whose blood markers confirmed they had been at risk for the disease and combined them with the feces of the at-risk people to search out the bacteria that had been tagged by the antibodies.
To additional take a look at their speculation, the researchers used animal fashions to host the newly found bacteria. Those experiments confirmed that not solely did the bacteria cause the animal fashions to develop the blood markers discovered in people at risk for RA; however a few of the fashions confirmed growth of full-blown RA as properly.
“Our collaborators led by Drs. Eddie James and Jane Buckner of Benaroya Research Institute confirmed that the T cells in the blood of people with RA will respond to these bacteria, but people who are otherwise healthy do not respond to these bacteria,” Kuhn says. “Through studies in humans and animal models, we were able to identify these bacteria as being associated with the risk for developing RA. They trigger an RA-like disease in the animal models, and in humans, we can show that this bacterium seems to be triggering immune responses specific to RA.”
A brand new goal for RA
If the distinctive species of bacteria is certainly driving the immune response that results in RA in people already at risk for the disease, Kuhn says, it may be attainable to focus on the bacteria with medicine to stop that response from taking place.
“The next thing we want to do is identify, in larger populations of individuals at risk for RA, if these bacteria correlate with other genetic, environmental, and mucosal immune responses, and then ultimately, the development of RA,” Kuhn says. “Then we could say, ‘This is a marker that’s useful in helping predict who will go on to develop RA,’ and apply prevention strategies. The other opportunity there is that if we can understand how it is triggering these immune responses, we might be able to block the bacteria’s ability to do that. “
Studying the trigger mechanism
The analysis took 5 years to conduct and analyze, Kuhn says, helped alongside by people who found they had been at risk for RA and volunteered to assist the analysis effort. Eventually the researchers need to look at precisely how the bacteria triggers the immune response, in addition to totally different strategies of stopping the response from taking place.
“There are a lot of different technologies that are just starting to come out that could selectively target a bacterium in the gut microbiome, for example, to prevent it from having immunogenic effects on the host,” she says. “For a long time, people have thought that antibiotics could be a useful therapy for RA, but rather than the sledgehammer effect of a traditional antibiotic that’s going to wipe out a large group of bacteria, we might be able selectively target this bacterium or its effects.”
