Graft Survival and Immune Regulation of Pancreas Allograft Recipients Induced With Thymoglobulin, Sirolimus, and Cyclosporine

Abstract

Background Our objective was to determine the impact of thymoglobulin–sirolimus–cyclosporine immunosuppression on the alloimune response of pancreas–kidney transplant recipients. Methods Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. A subset of 10 recipients were also enrolled in a study to measure immune responsiveness. Flow PRA–determined HLA antibody, donor-specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor cell assays were performed at various timepoints during the first posttransplant year. Results One-year patient, kidney, and pancreas survivals were 97%, 94%, and 92%, respectively. There was 1 death due to sepsis, and 1 kidney and 2 pancreas graft losses. There were no acute rejection episodes. Recipients in the immune-monitoring study displayed depression of CD3, CD4, and CD8 counts (<80%) until 3 months posttransplant. At transplantation, 9 of 10 patients displayed <10% class I HLA antibody. By 3 months, 7 of 10 showed a transient elevation in class I HLA antibodies, with 2 patients expressing >80% flow PRA. At transplant 1 patient was FCXM-positive, whereas, by 3 months posttransplant, 2 of 10 patients demonstrated a positive FCXM. There were no clinical consequences to either the presence of HLA antibody or the positive FCXMs. By 6 months, 7 of 9 patients expressed immunoregulatory suppressor cell activity. Conclusions The absence of acute rejection events was likely due to inhibition of donor-specific immunity. Seventy percent of patients demonstrated an early non–donor-directed HLA antibody response that had no adverse effect on graft function and 78% of the patients displayed immunoregulatory suppressor cell function, probably contributing to the successful clinical outcome.