USC Researcher Lights Up The Immune System To Help Heart Transplant Recipients

December 10, 1998

A USC-led study shows that a new kind of therapy helps prevent rejection of heart transplants.

In an article appearing in the Dec. 10 New England Journal of Medicine, USC cardiothoracic surgeon Mark L. Barr, reports that adding a novel immunomodulatory therapy, called photopheresis, to standard anti-rejection therapy reduced the number of serious organ rejections, without increasing rates of infection.

"I expect that photopheresis in the future will be used for both prevention and treatment of rejection in patients who receive organ transplants," said Barr, associate professor of surgery, who led an international, multi-center trial of the therapy.

"It is a much more targeted therapy than the current triple-drug regimen that transplant patients receive. Instead of suppressing the entire immune system, photopheresis potentially allows us to suppress only those immune cells responsible for rejecting a donated organ," he said.

Rejection of donated organs is a problem for many transplant patients, despite being treated with three powerful immune system suppressants. And this treatment often brings another serious complication-infection with opportunistic infections such as the cytomegalovirus (CMV). Barr said that photopheresis may also provide an anti-viral effect.

"We showed that patients in the photopheresis group had decreased levels of CMV in the bloodstream, which supports the idea that the procedure helps the patient's own immune system clears the virus," he said.

Photopheresis involves taking blood from patients, sorting out blood rich in immune cells called T-lymphocytes, or T-cells, that play an important role in mounting a defense against foreign molecules. For each patient, Barr and his colleagues then treated these T-cells, which specifically recognize and attack the donated organ. The T-cell attack is what causes rejection.

These T-cells were then inactivated by adding a drug, called methoxsalen, and exposing the mix to a UV-A light box, similar to the light used in tanning salons, Barr said. When the drug is activated by light, it binds to the T-cells and eventually kills the cells.

Each patient then received an injection of their own inactivated cells were then re-injected into the patient. Photopheresis "changes the way the body views its own cells, so that the immune system will recognize the very cells that are attacking the transplanted organ," Barr said.

In the study, a total of 60 heart transplant patients were randomly assigned to receive either photopheresis (with standard therapy) or standard therapy alone. The patients treated with photopheresis were more than twice as likely to have no rejection episodes than the patients in the control group. Also, the patients receiving standard therapy alone were over two-and-a-half times more likely to have multiple rejections after transplantation.

The photopheresis group had 0.9 acute rejection episodes per patient, while the control group had 1.4, a statistically significant difference. Researchers found no difference in survival in the two groups.

"We see this study as proof of principle, that photopheresis works to change the complicated immune response of transplant patients," said Barr, who first began studying the use of this novel therapy for transplantation 12 years ago.

"This study has major implications for many diseases that affect large populations of patients. Our results combined with additional experience with this technology suggest that this therapy could be used to treat a variety of autoimmune diseases, including inflammatory bowel disease and ulcerative colitis. It may also have a dramatic impact on the treatment of potentially lethal complications of bone marrow transplantation, such as graft vs. host disease, as well as in other solid organ transplants, including lung, small bowel and kidney."

Barr said that outside of the present study, he and other investigators have successfully used photopheresis in transplant patients who have had life-threatening rejection episodes despite aggressive treatment with standard anti-rejection therapy.

"Some of our patients have clearly been saved by this therapy," he said.

University of Southern California

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