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Genes hold the key for transplant recipients
By Bijal P. Trivedi

Researchers at the University of Pittsburgh have found that screening transplant recipients for certain genes may predict which patients are prone to rejection, alerting doctors to carefully tailor their immune suppressing drug therapy. The study was presented at the Transplant 2000 meeting that was held in Chicago from May 13-17.

‘In the future there may be thousands of genes that will be used to predict the success of a transplant.’

The greatest risk when transplanting an organ from one body to another is transplant rejection. The immune system sees a new organ as a foreign invader that must be destroyed, or rejected, and mobilizes cells to attacks the transplant. The Pittsburgh researchers have studied some genes that may predict the severity of the immune response against new tissue.

Heart tissue samples taken from 76 children who had heart transplants within the last ten years were examined under the microscope to gauge tissue damage; an indicator of whether the body had accepted the new heart. Each of the children in the study was then classified as either a rejecter or non-rejecter. Rejecters experienced more than one episode of organ rejection whereas the others with zero or mild immune responses were considered non-rejecters. "We looked at the non-rejecters and rejecters and asked whether patients within each group had similar genes," says Adriana Zeevi, of the University of Pittsburgh.

‘The genes you are born with are what's really important.’

Zeevi and her colleagues focused on four genes, which are important for triggering immune and inflammatory responses: interleukin-10 (IL-10), interleukin-6 (IL-6), tumor growth factor-b (TGF-b), and tumor necrosis factor-a (TNF-a). Each of these genes has a couple of variations that effect how much protein is produced from each one. The combinations of these genes determine how a patient's immune system will respond to a transplant.

By identifying the specific version of each of the four genes and creating a genetic profile for each of the 76 heart transplant recipients, Zeevi found that genes producing low amounts of the TNF-a protein and high amounts of the IL-10 protein are associated with a good response to the new heart.

"The results make sense," says Zeevi. Because TNF-a increases inflammation, low levels of this protein would lessen the chance of rejection. High levels of IL-10, which dampens immune reactions, also reduce the chance of rejection.

"The genes you are born with are what's really important," says Zeevi. If the genes indicate that one person has the genetic profile of a rejecter, for example, then doctors are aware of the risks faced by that patient and can change the drug therapies accordingly.

"In the future there may be thousands of genes that will be used to predict the success of a transplant. The immune system is complex, and the factors determining a successful transplantation may vary depending on the organ," says Zeevi.

The Pittsburgh study also profiled the four genes in 29 heart donors and 50 controls. "We still don't know the importance of the donor genes, so we must continue to do more work," says Zeevi.

Tailoring drugs based on a person's genes is part of the rapidly evolving field of pharmacogenomics.

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Awad, M.R. et al. The effect of cytokine gene polymorphism on pediatric heart allograft outcome. Transplant 2000: 1st joint meeting of the American Society of Transplant Surgeons and the American Society of Transplantation. Chicago, Illinois, May 13-17, 2000.

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