Rheumatoid arthritis (RA) is a debilitating autoimmune condition that affects millions of people across the globe. The ultimate cause of RA is largely mysterious. While researchers have long suspected that the microbiome influenced the development of the disease, the specific microbe has eluded identification.
Now, in a recent Science Translational Medicine paper, researchers reported a strain of bacteria that may drive RA development. Some people at risk for the disease have antibodies against this bacteria, and activation of T cells was more prevalent in people with RA than in healthy controls. Perhaps even more intriguingly, mice, given this bacterium, developed a condition similar to human RA.
Identifying this bacterium was no simple task. First, the research team, a collaboration between scientists at the University of Colorado, Stanford University, and the Benaroya Research Institute, screened blood donated by people at risk for RA or with early-stage RA for RA-related autoantibodies.
Then researchers tested whether any of these autoantibodies also targeted human intestinal bacteria. They mixed the antibodies with bacteria from stool samples donated by healthy people and people with RA. They then sequenced the bacterial species to which the autoantibodies attached. These RA antibodies cross-reacted with many species of bacteria, largely from Lachnospiraceae or Ruminococcaceae, two closely related families.
To study these species in more detail, researchers cultured bacteria from the stool of an individual who had high levels of these two bacterial families present. Two types of bacteria, which they called isolates 1 and 7, emerged as potential candidates for driving RA development. Compared to isolate 1, isolate 7 was a more potent activator of T cells in blood from RA patients.
To find out if isolate 7 bacteria actually caused disease, scientists fed the bacteria to mice. Kristine Kuhn, a study coauthor and rheumatologist at the University of Colorado, said that she didn’t expect anything to happen when the team gave the mice the bacteria without another agent to disturb the immune system.
While other bacteria have previously been associated with human RA, Subdoligranulum is so far unique in its ability to cause RA-like symptoms in mice without the addition of another immune insult.
The similarities between the mice and human RA patients extended beyond what could be seen with the naked eye. “There were antibodies getting into the joints, much like we see in rheumatoid arthritis,” said Kuhn. “So, we started to profile the antibodies that were in the serum of the mice and we found that a lot of those antibodies targeted the same proteins that are targeted in rheumatoid arthritis.”
Rabi Upadhyay, a medical oncologist who studies the microbiome, immunity, and cancer at the NYU Grossman School of Medicine and was not involved in this work, said that while this study convincingly demonstrated that this species could produce an RA-like condition in mice, it may be too soon to pin all the blame on Subdoligranulum alone since the study didn’t necessarily rule out other species.
In keeping with this, the researchers only found this strain in 16.7 percent of people at risk or with early-stage RA, indicating that this strain is likely not the sole driver of disease.
Currently, there are no therapies that can prevent or cure the disease, and immunosuppressant treatments that alleviate symptoms can have dangerous side effects.
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Dr. Eric L Reese I
Dr. Eric L. Reese is a 25+ year veteran in the life sciences industry focusing primarily on sales, marketing and business development for startup companies with disruptive technologies. Also, Dr. Reese has authored articles and presented globally on the utility of market-driven applications approaches to sales and marketing for the life sciences market space. To date Dr. Reese has spearheaded over 50+ industry collaborations focused on market development and sales growth utilizing his market-driven applications approach for the life sciences market space.