A study released Tuesday by scientists at The Scripps Research Institute in La Jolla could lead to major changes in the way patients with transplanted organs are treated in the future to prevent rejection.
In the study published in the American Journal of Transplantation, the researchers analyzed 234 kidney transplant biopsies and discovered that around 80 percent of the genes expressed in cases of early, acute rejection were also present in instances of chronic, much later rejections.
Acute and chronic rejections were thought to be separate conditions, but now appear to be difference stages along the same arc, the scientists say. About half of kidney transplants are rejected within 10 years, forcing patients onto dialysis, according to TSRI.
“For our transplant population, this is a major new understanding of the molecular basis of immune rejection that challenges the field to reconsider its current paradigms and has multiple immediate and actionable therapy implications for patients,” said Dr. Daniel Salomon, director of the Laboratory for Functional Genomics at TSRI. “The insights here most likely apply to liver, heart and lung transplants, too.”
He said the research shows that almost all transplant organ failure is due to inadequate suppression of the immune system, so that post-transplant patients can potentially be treated with the same therapies in order to prevent rejection.
“The new view that emerges from this research is that almost all transplant organ failure is due to inadequate immunosuppression, and with that understanding comes a potential for a major change in the practice of post- transplant drug therapy,” said Salomon, who is also medical program director of the Scripps Center for Organ Transplantation.
The researchers said more frequent biopsies could catch the body’s rejection of transplanted kidneys earlier than they are now.
Their study found a kind of kidney damage and scarring called interstitial fibrosis and tubular atrophy that could be a clue of approaching kidney rejection. Previous studies found that the presence of IFTA and inflammation — as seen under a light microscope — correlated with an increased risk of rejection. But IFTA on its own has been seen as evidence of a past injury, not active rejection, and is rarely treated.
“There was injury and inflammation there, just like in acute rejection patients — we just weren’t able to see it with the light microscope,” said Brian Modena, the first author of the study. “If you catch that early, you might potentially prevent chronic rejection. That would be a hugely positive benefit for our patients.”
TSRI reported that genetic expression profiling also proved to be a good tool for detecting subclinical acute rejection, which is active in about 20 percent of transplant patients in their first year, but impossible to suspect or diagnose until progression to clinical rejection.
Numerous other researchers took part in the study, including representatives of the Mayo Clinic, Northwestern Comprehensive Transplant Center in Chicago, and the University of Michigan. The study was funded by the National Institutes of Health.
—City News Service
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