Gut bacteria may be a potential therapeutic target for rheumatoid arthritis

Researchers at the University of Colorado (CU) School of Medicine have found that a type of bacteria found in the gut may be responsible for
triggering people at risk for rheumatoid arthritis (RA).

The results of the study, "cloned IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identified a form published in the journal Science Translational Medicine, led by Kristine Kuhn, MD
, associate professor of rheumatoid arthritis.
"

"The mucosal origin hypothesis of rheumatoid arthritis (RA) proposes that mucosal immune responses play a central role
in the initiation or continuation of systemic autoimmunity that accompanies disease development," the researchers wrote.
However, in rheumatoid arthritis, the link between mucous membranes and systemic autoimmunity is unclear
.
Using monoclonal autoantibodies derived from plasma antibodies of the IgG family of dual immunoglobulin A (IgA) and IgG families, from the peripheral blood of individuals at risk for RA, we determined cross-reactivity
between RA-associated autoantigens and the closely related Lachnospiraceae and Ruminococcaceae bacterial groups.
”

"The work, co-led by Kevin Deane, Kristen Demuelle and Mike Holers of the University of California, helped establish that we can determine who is at risk for rheumatoid arthritis based on serological markers that can be present in the blood for many years
before diagnosis," Kuhn said.
When they look at these antibodies, one is the normal type of antibody that we usually see in circulation, but the other is the antibody that we usually associate with our mucosa, whether it is the oral mucosa, intestinal mucosa, or lung mucosa
.
We began to wonder, 'Is there something at the mucosal barrier that causes rheumatoid arthritis?'"

Researchers at the University of Colorado took antibodies produced by immune cells from individuals whose blood markers showed they were at risk and mixed them with the feces of individuals at risk to look for antibody-labeled bacteria
.

The researchers also used animal models to host newly discovered bacteria
.
They observed that bacteria not only gave birth to the blood markers found in individuals at risk of rheumatoid arthritis in animal models; But some models also show the full development of
rheumatoid arthritis.

If this unique bacterium does drive the immune response in individuals at risk of causing rheumatoid arthritis, Kuhn said, it may be possible to target the bacteria with drugs to stop that reaction from happening
.

"The next step for us to do is to determine whether these bacteria are associated with other genes, the environment and mucosal immune responses in larger populations at risk of rheumatoid arthritis, and ultimately determine the development of
rheumatoid arthritis," Kuhn said.
Then we can say, 'This is a marker that helps predict who will develop rheumatoid arthritis,' and apply prevention strategies
.
" Another opportunity is that if we can understand how it triggers these immune responses, we may be able to block the bacteria's ability
.
”

"There are a lot of different techniques that are just starting to emerge that can selectively target bacteria in the gut microbiome, for example, to prevent it from having immunogenic effects
on the host," she said.
It has long been thought that antibiotics may be an effective treatment for rheumatoid arthritis, but unlike the sledgehammer effect of traditional antibiotics, which destroy a large host of bacteria, we may be able to selectively target this bacteria or its effects
.
”