Test Identifies Patients at Risk for Severe Organ Rejection, Report University of Pittsburgh Researchers at International Heart and Lung Transplantion Meeting
WASHINGTON, D.C., April 13, 2002 — A simple blood test takes much of the guesswork out of predicting who is at risk for severe organ rejection, according to results of two University of Pittsburgh studies presented at the 22nd Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation.
The test, referred to as ELISA (enzyme linked immunosorbent assay), indicates if a patient has specific antibodies that are trained to fight the presence of foreign antigens. According to results in studies of pediatric heart and adult lung transplant patients, ELISA does a better job of identifying patients with sensitized immune systems than the widely used, less sensitive test called PRA based on lymphocytotoxicity, which determines a percentage of panel reactive antibody. Having more reliable information may help clinicians tailor therapies to prevent rejection from actually occurring.
Indeed, in a retrospective study of pediatric heart transplant patients, four of the five "rejecters" were not identified as being sensitized by conventional PRA.
"ELISA identified children not considered sensitized by conventional PRA yet who are clearly at risk for rejection. Knowing in advance who may warrant more intense immunosuppression following heart transplantation is very useful clinical information," explained Sabrina Tsao, M.D., a cardiology fellow with the pediatric heart transplant program at the University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh.
Using blood samples of 36 patients obtained within a month before transplantation, researchers performed the ELISA test to see if results correlated with their actual clinical course. What they found was that ELISA determined 10 of 36 patients were susceptible to organ rejection. Five of these 10 (50 percent) actually developed severe rejection within a month, compared to three of the 26 (12 percent) negative-ELISA patients who developed rejection.
"Having this information before transplantation might have changed how we treated patients prone to rejection. While we'll want to study a greater number of patients, the results of this study suggest ELISA should be part of our routine clinical care," added senior author Steven A. Webber, MBChB, associate professor of pediatrics at the University of Pittsburgh School of Medicine and director of the pediatric heart and lung transplant program at Children's Hospital of Pittsburgh.
Interestingly, eight of the 10 ELISA-positive patients had congenital heart disease and were probably more sensitized to certain antigens because of blood transfusions received during past open-heart surgeries.
In a similar study involving 75 adult lung transplant patients who underwent ELISA testing after transplantation, six of 14 (43 percent) deemed positive developed persistent, acute rejection within the first 100 days of transplantation compared to nine of 61 (15 percent) who were negative. Similar results were obtained at follow-up periods up to a year.
"Screening with ELISA is a reliable, cost-effective method that may allow the identification of lung transplant recipients at high risk for persistent and recurrent cellular rejection, a known risk factor for chronic rejection," reported Alin Girnita, M.D., a transplant immunology fellow at the University of Pittsburgh School of Medicine. With chronic rejection, air cannot pass through the lung's bronchioles. Because it is difficult to treat, chronic rejection is considered one of the most serious complications in lung transplantation.
Added Adriana Zeevi, Ph.D., professor of pathology and surgery at the University of Pittsburgh Thomas E. Starzl Transplantation Institute and an author on both studies: "As the results indicate with the pediatric heart patients, this test is clearly useful before transplantation, but we should also consider making ELISA more routine after transplantation. Some patients, for reasons we do not fully understand, will develop anti-donor antibodies within weeks or months after transplantation. Using the ELISA method we can discriminate between the different types of antibodies, which can help guide therapy."
ELISA is a simple test that takes about four hours to obtain a positive or negative result. Blood drawn from the patient contains the patient's own unique antibodies, which are put into contact with known human leukocyte antigens (HLA), molecules on the surface of all cells that characterize each person as unique and enable the immune system to recognize both self and foreign antigens. If the patient's antibodies bind with any of the antigens, then the test is considered positive. ELISA can make further distinctions to identify between the two classes of HLA that the recipient is most sensitive to.