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The Cutting Edge

Understanding Organ-Transplant Rejection

Heart Blood-vesselUCLA RESEARCHERS HAVE PINPOINTED the culprit behind chronic rejection of heart, lung and kidney transplants. Published in the journal Science Signaling, their findings suggest new therapeutic approaches for preventing transplant rejection and sabotaging cancer growth.

The team focused on the mechanism behind narrowing of the donor’s grafted blood vessels, which blocks blood from reaching the transplanted organ. Starved of oxygen and other nutrients, the organ eventually fails, forcing the patient back on the transplant waiting list.

Earlier research by Elaine Reed, Ph.D., director of the UCLA Immunogenetics Center and professor of pathology at the David Geffen School of Medicine at UCLA, and colleagues showed that patients whose immune systems manufactured antibodies to their donor’s human leukocyte antigens (HLA) were at higher risk for chronic rejection. In this study, Dr. Reed and her group looked at how HLA molecules on donor tissue trigger signals that spark overgrowth of the cells lining the inner blood vessels of the grafted organ.

The scientists discovered that HLA’s ability to stimulate cell growth and movement depends upon a quid pro quo relationship with another molecule called integrin beta 4, which enables cells to survive and spread. “We suspect that integrin hijacks HLA and takes over its functions,” Dr. Reed says. “When we suppressed integrin, HLA was unable to make cells grow and move.” Conversely, when the team suppressed HLA, integrin could no longer support cells’ communication with their environment.

“What I’m excited about from a medical point of view is how our findings offer new therapeutic opportunities,” says Dr. Reed. “If we can identify ways to disrupt the relationship between HLA and integrin, we may be able to prevent chronic organ rejection in transplant patients.”

 





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