Graft survival and immune regulation of pancreas allograft recipients induced with thymoglobulin, sirolimus, and cyclosporine.
BACKGROUND
Our objective was to determine the impact of thymoglobulin-sirolimus-cyclosporine immunosuppression on the alloimmune 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.
Knight
R J
RJ
Division of Immunology and Organ Transplantation, University of Texas Medical School, Houston, Texas 77030, USA.
Kerman
R H
RH
Podder
H
H
Katz
S M
SM
Van Buren
C T
CT
Kahan
B D
BD
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D003140:Communicable Disease Control; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D018655:Lymphocyte Count; D015166:Monitoring, Immunologic / Q000379:methods; D016035:Pancreas Transplantation / Q000276:immunology*; D011183:Postoperative Complications / Q000517:prevention & control; D020123:Sirolimus / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000276:immunology
D000900:Anti-Bacterial Agents; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus