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Insight into transplant rejection might lead to novel prevention therapies

ORLANDO, Fla. -- A newly discovered means by which the body attacks transplanted organs might lead to novel methods of preventing the rejection response, research by Duke University Medical Center pulmonologists and transplant surgeons suggests. The finding sheds new light on the role of the innate immune system, the body's first line of defense, in the acute rejection of transplanted lungs.

Drugs targeting the immune reaction could help combat early lung rejection and its complications, thereby increasing patients' chances of survival following the surgery, the researchers said.

Lung transplant recipients with particular variants of a gene called TLR4, which is critical in the lung's defense against bacterial infection, were significantly less likely to suffer acute rejection of the organs, the team found. The researchers presented their results at the 100th International Conference of the American Thoracic Society on May 24, 2004. The work was supported by the National Heart, Lung, and Blood Institute, the National Institute of Environmental Health Sciences, and the Department of Veteran Affairs.

"Those patients with particular variants of the innate immune system gene have a sustained decrease in the frequency and severity of rejection," said Scott Palmer, M.D., medical director of the Duke University Medical Center Lung Transplant Program and lead author of the study. "The finding is consistent with the novel idea that innate immunity regulates the rejection of transplanted lungs."

The innate immune system plays a critical role in combating foreign invaders immediately after infection or exposure, before the body's adaptive immune system can recognize the invasion and launch its attack. While physicians have generally attributed organ transplant rejection solely to the adaptive immune system, the new work indicates an important role for the body's first line of defense, Palmer said.

Acute rejection occurs in 60 percent of
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-684-4148
Duke University Medical Center
24-May-2004


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