Researchers at the University of Colorado (CU) School of Medicine have discovered that a bacteria found in the gut may be responsible for triggering rheumatoid arthritis (RA) in people already at risk for the disease.
The findings, “Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum,” is published in the journal Science Translational Medicine and led by Kristine Kuhn, MD, PhD, associate professor of rheumatology.
“The mucosal origins hypothesis of rheumatoid arthritis (RA) proposes a central role for mucosal immune responses in the initiation or perpetuation of the systemic autoimmunity that occurs with disease,” wrote the researchers. “However, the connection between the mucosa and systemic autoimmunity in RA remains unclear. Using dual immunoglobulin A (IgA) and IgG family plasmablast–derived monoclonal autoantibodies obtained from peripheral blood of individuals at risk for RA, we identified cross-reactivity between RA-relevant autoantigens and bacterial taxa in the closely related families Lachnospiraceae and Ruminococcaceae.”
“Work led by co-authors 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 said. “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?’”
The CU researchers took the antibodies created by immune cells from individuals whose blood markers showed they were at risk for the disease and mixed them with the feces of the at-risk individuals to find the bacteria that were tagged by the antibodies.
The researchers also used animal models to host the newly discovered bacteria. They observed that not only did the bacteria cause the animal models to develop the blood markers found in individuals at risk for RA; but some of the models showed development of full-blown RA as well.
If the unique species of bacteria is indeed driving the immune response that leads to RA in individuals already at risk for the disease, Kuhn said, it might be possible to target the bacteria with medication to prevent that response from happening.
“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 said. “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.”
“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 said. “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.”
