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Researchers discover reasons for organ rejection

In this vasculopathic heart vessel, interaction between two specific molecules narrows blood vessels, causing a reduction of oxygen flow.

UCLA DEPARTMENT OF PATHOLOGY

By Sarah Khan

Nov. 24, 2010 1:11 a.m.

For patients whose organs have failed, an organ transplant often means another shot at a healthy life.

But more than 40 percent of organ transplants fail within one year. A patient’s antibodies will sometimes attack the foreign organ, a phenomenon that has been little understood by researchers up to this point, said Elaine Reed, director of the UCLA Immunogenetics Center.

On Tuesday, UCLA researchers published the results of a five-year study that uncovers previously unknown reasons for why organs are rejected by their host body, said Reed, a co-author of the study.

The key lies with two molecules, human leukocyte antigen and integrin beta-4, which depend on each other to incite the organ rejection, she said.

The interaction of human leukocyte antigen and integrin ignites a negative immune response in a patient with an organ transplant, Reed said. The patient’s body then produces antibodies to shut down the functioning organ, often by overgrowing blood vessel cells and restricting the organ’s access to oxygen and other nutrients.

This mechanism may explain why organ rejection is difficult to reverse, Reed said.

“Once the patients start making the antibodies, you can’t stop it,” she said. “Chronic rejection is the major problem.”

Although it is possible to live without an organ like a kidney, there are not many options for a patient whose body rejects a heart, liver or lung. In these cases, retransplant is often the choice for survival, Reed said.

Waiting periods to receive organs can be so long that patients sometimes die on the wait list, said Murray Kwon, a heart transplant surgeon at Ronald Reagan UCLA Medical Center.

The study doesn’t stop at solving the mystery of organ rejection.

The team is also looking at applying the research to cancer prevention and treatment, said Xiaohai Zhang, lead author of the study and a postgraduate researcher in pathology and lab medicine at UCLA.

In the lab, Zhang prevented integrin from combining with human leukocyte antigen and, as a result, noticed that blood cells did not grow as much, he said.

It may be possible to do the same thing to tumors to keep blood vessels from sprouting inside them, he said.

Although the findings are not ready to be developed into drugs or therapies, the findings provide hope for organ transplant and cancer patients who otherwise have few options for a healthy life, Reed said.

“We have to understand the mechanism before we develop the therapy,” she said.

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