Pancreas transplantation utilizing thymoglobulin, sirolimus, and cyclosporine.
BACKGROUND
This study aims 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. Ten 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 during the first posttransplant year.


RESULTS
One-year patient, kidney, and pancreas graft survivals were 97%, 94%, and 92%, respectively. There was one death and three graft losses. There were no acute rejection episodes. Recipients in the immune-monitoring study (n=10) displayed>80% depression of CD3, CD4, and CD8 (+) cell counts up to 3 months posttransplant. At transplantation 9/10 patients displayed<10% class I and no class II HLA antibody. By 3 months, 7/10 monitored recipients showed a transient elevation in class I HLA antibodies, including 2 patients who expressed>80% Flow PRA. One patient was pretransplant FCXM positive, whereas by 3 months posttransplant 2/10 patients demonstrated a positive FCXM. There were no clinical consequences of the presence of HLA antibody or the positive FCXMs. By 6 months, 7/9 patients demonstrated immunoregulatory suppressor cells.


CONCLUSIONS
The absence of acute rejection events was likely due to inhibition of donor-specific immunity by the immunosuppressive regimen. 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 monitored patients displayed immunoregulatory cells probably contributing to the successful outcomes.
Knight
Richard J
RJ
Division of Immunology and Organ Transplantation, The University of Texas Health Science Center, Houston, TX 77030, USA. richard.j.knight@uth.tmc.edu
Kerman
Ronald H
RH
Zela
Scott
S
Podbielski
Jeannette
J
Podder
Hemangshu
H
Van Buren
Charles T
CT
Katz
Stephen
S
Kahan
Barry D
BD
D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D016572:Cyclosporine / Q000008:administration & dosage*; D003586:Cytomegalovirus Infections / Q000209:etiology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007518:Isoantibodies / Q000097:blood; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000276:immunology; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000961:Antilymphocyte Serum; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016572:Cyclosporine; D020123:Sirolimus