INTEGRAFT MONITORING OF REJECTION AFTER PROPHYLACTIC TREATMENT WITH MONOCLONAL ANTI-INTERLEUKIN-2 RECEPTOR ANTIBODY (BT563) IN HEART-TRANSPLANT RECIPIENTS

Background: Anti-interleukin-2 receptor monoclonal antibodies have bee n used successfully in the prevention of rejection in cardiac allograf ts in several animal models. Methods: In an open randomized study muri ne monoclonal CD3 antibody and BT563, a murine anti-interleukin-2 rece ptor monoclonal antibody, were given as rejection prophylaxis during t he first week after heart transplantation. Cyclosporine therapy was in itiated at the third postoperative day. Results: In half the BT563-tre ated patients an early rejection was histologically shown at week 1, w hereas heart transplant recipients treated with murine monoclonal CD3 antibody had a rejection incidence at week 1 of only 9%. During BT563 treatment CD25-positive cells (i.e., cells bearing the interleukin-2 r eceptor) were not detectable in peripheral blood. However, immunohisto logic studies of endomyocardial biopsy specimens taken 1 week after tr ansplantation showed the presence of CD25-positive cells within these specimens in 8 of 10 (80%) of patients with rejection. In patients wit hout rejection CD25-positive cells were present in the biopsy specimen s of only two of nine patients (22%). Reverse-transcriptase polymerase chain reaction studies on biopsy material showed the presence of mess enger RNA for the interleukin-2 receptor in all and for interleukin-2 in three of five (60%) of biopsy specimens of rejecting grafts. Conclu sions: Although CD25-positive cells were not detectable in peripheral blood during BT563 treatment, these cells were at the same time found to be present within 80% of the endomyocardial biopsy specimens from t he rejecting grafts. By initiating cyclosporine treatment at day 0, th e synergistic effect of combining cyclosporine and anti-interleukin-2 receptor monoclonal antibodies may result in a lower rejection inciden ce.