BY KRISTIN WEIDENBACH
More than 4,000 scientists, researchers and physicians interested in transplantation gathered in Rome Aug. 27 through Sept. 1 to attend the 18th International Congress of the Transplantation Society. Oscar Salvatierra Jr., MD, professor of transplant surgery and of pediatrics and director of adult and pediatric renal transplantation at Stanford and at Lucile Packard Children's Hospital, presided over this year's meeting.
As president, Salvatierra had the honor of presenting a gold commemorative medal to Pope John Paul II on behalf of the society. The pope chose the meeting as the venue to announce the Catholic Church's support for organ donation and transplantation. "There is a need to instill in people's hearts, especially in the hearts of the young, a genuine and deep appreciation of the need for brotherly love, a love that can find expression in the decision to become an organ donor," the pope said in his speech.
In the 34-year history of the society, Salvatierra is only the sixth surgeon from the United States to become president. He was elected in a ballot wherein the society's 3,000 members from 67 countries each cast a vote for one of the four presidential nominees.
"Unlike most societies, where the president is elected by a core group, this is a totally democratic process," said Randall Morris, MD, professor of cardiothoracic surgery and a fellow society member. "It means he's very well respected and has made tremendous contributions to the society."
Morris, who was elected a council member of the transplantation society at the meeting, traveled to Rome with colleagues from his laboratory to make several conference presentations. One of the talks from his group addressed the relatively new field of pharmacodynamics, which measures how immunosuppressive drugs affect immune system cells travelling in the blood. "We are very interested in measuring immune function in very small samples -- a drop of blood," said Morris.
Physicians must continually monitor how a transplant recipient's cells are responding to immunosuppressive drugs administered to prevent rejection of the new organ. "Different patients' immune systems are more or less sensitive to the same drug dose," explained Morris. "So my immune system may be over-suppressed at the same drug level at which you're under-suppressed and at risk of rejection."
To maintain the correct drug dosage and watch for signs of rejection, physicians test the immune system's white blood cells in each patient, and they collect cells directly from the transplanted organ in a procedure known as a biopsy. But there are drawbacks to the commonly accepted protocols. Biopsies involve inserting a long, thin needle into the transplanted heart or kidney and can be traumatic for a patient. A blood draw is less invasive, but the current method -- separating the white cells from the remainder of the blood and studying them in isolation -- can bias the results of the test and mask the effects of the drug.
Morris and his colleagues developed a method to study the white cells without separating them from whole blood. They have shown that changes they see in white cells are reliable indicators of changes occurring in cells within a transplanted heart or kidney. Using the new method, Morris and his colleagues have learned more about how the human immune system responds to immunosuppressive drugs. Researchers "have had a simplistic and naive belief about how drugs work in the body based on how they work in the test tube. This new technology expands our knowledge of how the drugs actually work in a more relevant setting," said Morris.
The researchers hope that the simplified blood test will allow physicians to fine-tune immunosuppression for each individual. Using a small drop of blood, doctors may be able to measure how the immune system is responding to different doses of drugs without needing to subject a patient to a biopsy or to rely on the potentially confounding results derived from isolated cells.
Minnie Sarwal, MD, PhD, assistant professor of pediatrics and a colleague of Salvatierra's is also seeking ways to detect and monitor rejection without having to jab patients with a biopsy needle. She is working with researchers in the laboratory of Patrick Brown, MD, PhD, associate professor of biochemistry and a Howard Hughes Medical Institute investigator, to develop DNA-based methods to diagnose rejection.
Sarwal agrees with Morris that currently there is no way to diagnose rejection via a simple blood test. Physicians look for changes in the blood that indicate a problem in the transplanted organ, but the only way to confirm rejection is to perform a biopsy, she said. Sarwal is surveying thousands of human genes, searching for those that vary their activity in response to transplantation-associated changes in the immune system. Such changes can signal transplant rejection or problems caused by too much immunosuppression. Sarwal hopes to find a handful of genes that will reveal when rejection is occurring and what kind of rejection it is.
Different kinds of rejection, said Sarwal, require different types of treatment. Physicians first choose steroid drugs to treat the most common kind of rejection. If the patient fails to improve, the doctor will switch to antibody therapy to stem rejection. "Trying different treatments sequentially we lose a lot of time during which quite a lot of injury [to the organ] is ongoing," said Sarwal.
So far, Sarwal and her colleagues have found more than 1,000 genes in normal cells that change their activity when organ rejection occurs. They hope to focus on five to 10 highly informative genes that will form the basis of a rapid blood test. Sarwal presented the team's initial findings as an invited speaker at the Rome meeting.
More than a dozen Stanford faculty
and residents presented research findings at the meeting. As
president of the society, Salvatierra said he was proud to attend
the meeting with so many accomplished fellow researchers. "What
makes us unique here at Stanford, is the amalgamation of
outstanding clinical programs and outstanding basic research
efforts," said Salvatierra. "We're really at the cutting edge."
SR