Unique gut bacteria may be responsible for triggering rheumatoid arthritis in at-risk individuals

Unique gut bacteria may be responsible for triggering rheumatoid arthritis in at-risk individuals

Researchers at the University of Colorado School of Medicine have discovered that a unique bacteria in the gut may be responsible for triggering rheumatoid arthritis (RA) in people who are already at risk for the autoimmune disease.

Kristine Kuhn, MD, PhD, associate professor of rheumatology, led a team of researchers from the Division of Rheumatology on the study, published Oct. 26 in the journal Science Translational Medicine. Meagan Chriswell, a student at the CU School of Medicine, is the lead author of the paper.

“Work led by co-authors Drs. Kevin Deane, Kristen Demoruelle and Mike Holers here at CU has helped establish that we can identify people at risk for RA using serological markers and that these markers can be present in the blood many years before diagnosis,” says Kuhn. "When they looked at these antibodies, one was the normal class of antibodies that we normally see in the circulation, but the other is an antibody that we normally associate with our mucosa, be it the oral mucosa, the intestinal mucosa, or the lung mucosa. We started to wonder, 'Could there be something at a mucosal barrier site that could be driving RA?'"

Discovery of a new bacterium

The CU researchers, with the help of a group led by Bill Robinson, MD, PhD, at Stanford University, took the antibodies produced by immune cells from people whose blood markers showed they were at risk for the disease and mixed them with the feces of the at-risk people to find the bacteria marked by the antibodies.

To further test their hypothesis, the researchers used animal models to house the newly discovered bacteria. These experiments showed that the bacteria not only caused the animal models to develop the blood markers found in people at risk for RA; but some of the models also showed development of full-blown RA.

Our employees, led by Dr. Eddie James and Jane Buckner from the Benaroya Research Institute confirmed that the T cells in the blood of people with RA respond to these bacteria, but people who are otherwise healthy do not respond to these bacteria. Through studies in humans and animal models, we were able to identify these bacteria as being associated with the risk of developing RA. They trigger an RA-like disease in animal models, and in humans we can show that this bacterium appears to trigger RA-specific immune responses.”

Kristine Kuhn, MD, PhD, associate professor of rheumatology

A new goal for RA

If the unique species of bacteria actually drives the immune response that leads to RA in people who are already at risk for the disease, Kuhn says it might be possible to attack the bacteria with drugs to prevent that reaction.

“Next, we want to identify in larger populations of individuals at risk for RA whether these bacteria correlate with other genetic, environmental and mucosal immune responses and ultimately with the development of RA,” says Kuhn. "Then we could say, 'This is a useful marker for predicting who will go on to develop RA,' ​​and use prevention strategies. The other possibility is that we could understand how it triggers these immune responses and be able to block the bacteria's ability to do that."

Investigation of the trigger mechanism

The research took five years to conduct and analyze, Kuhn says, supported by people who discovered they were at risk for RA and volunteered to support the research effort. Ultimately, the researchers want to study exactly how the bacterium triggers the immune response, as well as different methods to prevent the reaction.

“There are many different technologies that are just coming to market that could, for example, selectively target a bacterium in the gut microbiome 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 instead of the sledgehammer action of a traditional antibiotic that will wipe out a large group of bacteria, we could selectively attack this bacterium or that effect."

Source:

University of Colorado Anschutz Medical Campus

Reference:

Chriswell, ME, et al. (2022) Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of subdoligranulum. Science Translational Medicine. doi.org/10.1126/scitranslmed.abn5166.

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