University of Pittsburgh researchers reveal possible screening to identify transplant patients who are 'rejecters'

May 13, 2000

CHICAGO, May 14 - Patients prone to rejection could be screened and their immunosuppression tailored to prevent serious episodes that could result in graft loss, according to a University of Pittsburgh study that classified pediatric heart transplant patients by their genetic profiles of certain hormones involved in the immune response. Results of the study were presented at Transplant 2000, the first combined scientific sessions of the American Society of Transplant Surgeons and the American Society of Transplantation. The meeting is being held May 13 - 17 at the Sheraton Chicago Hotel and Towers.

"These profiles could be used by the transplant team to help determine the best immunosuppressant regimen for their patients," said Adriana Zeevi, Ph.D., professor of pathology and surgery at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute.

Using a polymerase chain reaction method that detects the unique profiles of genes, 81 heart recipients, 29 organ donors and 50 control patients were cytokine-genotyped. Cytokines are hormone-like substances that cells use to communicate with each other and that modulate immune activity.

Those recipients who had multiple acute rejection episodes-- referred to as rejecters -- had a markedly different profile of cytokine genes (lower levels of Interleukin-10, or IL-10) than did those who experienced few episodes (higher levels of IL-10 and low levels of Tumor Necrosis Factor-alpha, or TNF-a). Donor cytokine genotype had little correlation with rates of rejection.

Because the screening may prove useful as a predictor factor for the frequency of rejection, Dr. Zeevi's colleagues plan to evaluate its value in a protocol that involves weaning patients off immunosuppression. Typically, transplant patients are required to take anti-rejection drugs for the rest of their lives. Such drugs can cause serious complications, such as tumor growth, and make patients more susceptible to infections.

In a study also presented today, George Mazariegos, M.D., assistant professor of surgery at the Starzl Transplantation Institute, reported that nearly a third of the 120 patients enrolled in the physician-controlled protocol have been completely weaned. Weaning was stopped in another third who experienced acute rejection.

"While these cases were successfully treated, usually by reinstating their previous levels of immune suppression with or without steroid therapy, and no grafts were lost, it would be extremely helpful to be able to predict in advance which patients we can successfully wean," said Dr. Mazariegos.

Nearly 70 presentations on clinical and basic science research findings are being presented by University of Pittsburgh transplant researchers at Transplant 2000. Other papers include results using livers from nonheart-beating donors, the causes and rates of retransplantation in 4,000 liver transplants at the Pittsburgh center and an analysis of waiting times and tumor growth for patients with hepatocellular carcinoma.
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CONTACT: Lisa Rossi or Maureen McGaffin
PHONE: (412) 624-2607
FAX: (412) 624-3184
E-MAIL: RossiL@msx.upmc.edu
Mcgaffinme@msx.upmc.edu

University of Pittsburgh Medical Center

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