New Pitt Project To Examine Transplanted Organ 'Tolerance'

Will Study Why Some Patients Lose Need For Anti-Rejection Drugs

By Anita Srikameswaran

Post-Gazette Staff Writer

When Thomas Collins received a life-saving liver transplant 11 years ago, his doctors told him he'd have to take anti-rejection drugs for the rest of his life.

He knew the powerful medications would suppress his immune system, making him susceptible to infections and the growth of tumors after long-term use. But when you're in a fight for your life, he explained, "you're just happy that you have the opportunity to take the drugs."

A few years ago, however, Collins joined a study at the University of Pittsburgh in which liver recipients were weaned off their medications. The Confluence man had no problems when the drugs were reduced and, now 61, he hasn't taken any for almost three years.

Transplant researchers, with help from the National Institutes of Health, aim to find out what makes transplant patients like Collins so special. They will study a small group of these drug-free patients in an effort to devise tests that will help identify other liver recipients who might be safely weaned from their anti-rejection drugs.

Medications like cyclosporine and steroids are used to protect donor organs from being attacked by the recipient's immune system. But in some cases, the immune system declares a truce with the foreign tissue. The transplant patient is said to be tolerant to the donor organ, making the drugs unneccessary.

Right now, doctors don't have lab test to show if a patient has achieved tolerance or not, so withdrawing immunosuppressant drugs can be risky, explained Angus Thomson, project investigator and a professor at the UPMC Starzl Transplantation Institute.

"That is an important factor propelling this study," he said. "The mission of our sponsors ... is to be able to predictably achieve tolerance in organ transplantation."

Thomson's quest to find lab markers of tolerance has been awarded more than $700,000 by the Immune Tolerance Network, a $144 million project supported by the National Institutes of Health and the Juvenile Diabetes Foundation International.

Thomson and co-investigator Adriana Zeevi will examine white blood cells that regulate immune responses from transplant patients who are tolerant of their donor organs. The researchers will also study the cytokines, or chemical signals, released by the white cells and look for subtle genetic differences in cytokine makeup.

This data will be compared to that from transplant patients who rejected their donor organs after withdrawal of immunosuppressants because of toxicity, infection or medical complications. Similar tests will be performed on blood samples taken from organ recipients while they are being carefully weaned from the drugs.

Some of the tests will be performed by collaborators at Case Western Reserve University and the University of Wisconsin -- Madison.

Pitt has been at the forefront of immune tolerance research. Transplant surgeon Dr. George Mazariegos has been leading a study of liver transplant patients who are being weaned off of anti-rejection drugs, providing a pool of 40 patients who could participate in the new project.

"As one looks around the world, stable transplant recipients off all immunosuppression is a very rare commodity indeed," Thomson said. Transplant patients should never reduce or stop their medications on their own, he cautioned.

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This article posted November 15, 2000.