What is already known
Rheumatoid arthritis is an autoimmune inflammatory disorder that damages joints. The immune system of people at risk for the condition produces autoantibodies, or antibodies directed against one or more of the individual’s own proteins, before the development of clinical disease. However, the triggers of the disease as well as the source of harmful autoantibodies have remained unclear.
What this research adds
Researchers analyzed autoantibodies from people at risk of developing rheumatoid arthritis and individuals in the early stages of the condition. They found that the antibodies reacted not only to rheumatoid arthritis antigens, but also to the gut bacteria Lachnospiraceae and Ruminococcaceae. One Subdoligranulum strain isolated from a person with rheumatoid arthritis was able to bind with autoantibodies and activate inflammatory immune cells. Mice colonized with the Subdoligranulum strain showed signs of rheumatoid arthritis, including inflamed joints.
Conclusions
The findings suggest that a specific strain of Subdoligranulum can drive the production of autoantibodies in rheumatoid arthritis.
Rheumatoid arthritis — a debilitating disorder that damages joints — is one of the most common autoimmune conditions. A species of bacteria found in the gut microbiota can drive the production of harmful autoimmune molecules in the early stages of rheumatoid arthritis, according to a new study done in mice and people with the disease or at high risk for it.
The findings, published in Science Translational Medicine, may inform therapeutic approached aimed at eliminating the gut bacteria that trigger the original immune response.
People at risk for rheumatoid arthritis produce autoantibodies, or antibodies directed against one or more of the individual’s own proteins, before the development of clinical disease.
Although previous research suggested that alterations in the gut microbiota are linked to rheumatoid arthritis, the triggers of the disease as well as the source of harmful autoantibodies have remained unclear.
To assess whether gut microbes could trigger the condition by generating local immune responses, Kristine Kuhn at the University of Colorado and her colleagues analyzed autoantibodies from people with rheumatoid arthritis and those at high risk for developing the disease.
Antibody bindings
The researchers collected blood samples from four people with a risk of developing rheumatoid arthritis and two people in the early stages of the condition.
The team found that the antibodies reacted not only to rheumatoid arthritis antigens, but also to gut bacteria. More than 50% of the microbes bound by the antibodies were from the bacterial families Lachnospiraceae and Ruminococcaceae.
To investigate immune responses to specific species of Lachnospiraceae and Ruminococcaceae, the researchers isolated gut microbes from a person with in rheumatoid arthritis who had more than 40% abundance of these bacterial families in their feces. One Subdoligranulum strain in particular was able to bind with autoantibodies and activate a class of inflammatory T cells.
Autoimmune responses
Mice colonized with the Subdoligranulum strain showed signs of rheumatoid arthritis, including inflamed joints and swollen paws. These animals also had increased blood levels of rheumatoid arthritis-related autoantibodies and TH17 cells. TH17 cells help B cells to make antibodies and recruit other immune cells to inflamed areas of the body — among other things.
The findings indicate that the Subdoligranulum strain, which the team called Subdoligranulum isolate 7, engages immune cells to trigger autoimmune responses in the tissue that keeps joints well lubricated.
“Our data suggest one pathway by which the intestinal microbiome and mucosal immune responses can lead to systemic autoreactivity and joint pathology that is potentially a pathway in human [rheumatoid arthritis],” the researchers say.
