You could one day be spared from ever experiencing the debilitating symptoms of rheumatoid arthritis (RA)—thanks to a new discovery that could help open the door to prevention.
It seems RA doesn’t just start when the pain begins but silently years earlier, along with new early-warning signs, scientists at the Allen Institute of Immunology have discovered in a seven-year study.
The research—conducted with the University of California San Diego (UCSD), the University of Colorado Anschutz Medical Campus (CU Anschutz) and the Benaroya Research Institute (BRI)—reveals people at risk of the autoimmune disease experience “dramatic” immune system changes long before they feel typical symptoms.
“Currently, once someone develops the swollen joints of RA, the disease is usually ‘forever’ meaning that they will need to be on treatments for life. Furthermore, worldwide, RA affects millions of people’s lives [1.5 million in the U.S.] and costs billions of dollars to manage,” study author Dr. Kevin Deane, rheumatology professor at CU Anschutz, told Newsweek.
“If we find ways to prevent the first swollen joints in RA, or even ‘reset’ the immune system in an at-risk stage, this could lead to people never getting full-blown RA—or having a much milder form of disease.”
The new research could help push forward proactive prevention and personalized medicine, rather than just reactive treatment.
“Our team discovered that during this ‘at-risk’ period where individuals look and feel healthy, their immune systems are dramatically different,” study author and investigator at the Allen Institute Mark Gillespie told Newsweek.
For years, researchers tracked people carrying ACPA antibodies, known biomarkers for individuals at risk for developing RA, and identified previously unknown factors associated with disease development.
“Individuals who are at risk for RA show widespread inflammation and signs of immune activity, including in B cells that produce the autoreactive antibodies that characterize RA, and the T cells that interface and instruct the B cells to make these antibodies,” Gillespie explained.
They also discovered immune changes in “naïve” T cells. “This is significant because these cells have not encountered any threats previously and may suggest that immune cells in individuals at risk for RA are already wired to respond in a determinantal manner.”
Overall, the early signs detected included widespread inflammation, immune cell dysfunction, cellular reprogramming, cells shifting into different states and expanding beyond normal levels and joint-like inflammation in blood.
These potential new signs could help doctors identify who among at-risk individuals are most likely to develop RA and lead to more targeted monitoring and earlier prevention.
“Rheumatoid arthritis is currently diagnosed as ‘full-blown disease’ when someone has a swollen joint and other features such as blood tests that include a test called ‘anti-CCP’,” said Deane.
“However, there are numerous studies that have shown that individuals can have abnormal blood tests such as anti-CCP for on average 3–5 years before they develop their first swollen joint. We call this period when someone has blood markers of RA, but no swollen joints, as an ‘at-risk’ period that can also be called ‘pre-RA.’”
As it proved challenging to find people who are at-risk for RA before symptoms, the study included testing people in health fairs and those for whom RA runs in their families.
“While anti-CCP is a strong risk factor for RA, not all anti-CCP+ people will get RA. With that in mind, the findings from this study can do two major things,” said Deane.
“The first is that these findings can help us pinpoint which anti-CCP+ people will actually develop ‘full-blown’ RA. Second, the biologic findings that help us identify who will get RA can also be considered as ‘targets’ for preventive interventions in future studies.”
There have already been some clinical trials conducted with the goal to prevent RA that have promising findings on some drugs to delay onset, according to the authors, though nothing has currently been approved.
“Hopefully, the findings from our new study will provide new insights into biologic development of RA that we can then take into new prevention trials for RA,” added Deane.
“Of course we will need careful follow-up studies, but one can envision that in the near future we would have an approach to RA that is similar to how we approach heart-attack prevention today where someone gets a blood test (like a cholesterol level, or anti-CCP) that helps predict risk and then is given an intervention (like a cholesterol-lowering medication, or an RA-directed therapy) to help reduce the risk of a heart attack (or full-blown RA).”
The team hopes their findings will directly support new ways to predict RA and potentially identify targets for prevention trials, along with further studies.
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