The Presence of Donor-Specific Human Leukocyte Antigen Antibodies Does Not Preclude Successful Withdrawal of Tacrolimus in Stable Renal Transplant Recipients

Abstract

Because of the adverse events associated with the administration of immunosuppressive drugs, reduction of immunosuppression after solid-organ transplantation is highly desirable provided that graft rejection is prevented. In our transplant center, we used an immunosuppression reduction regimen in stable renal transplant patients. The presence of human leukocyte antigen (HLA) antibodies has been negatively associated with transplant outcome. Therefore, we evaluated the impact of HLA antibodies on the occurrence of acute rejection after immunosuppression reduction. The presence and antigen specificity of HLA immunoglobulin G antibodies in serum samples were detected using enzyme-linked immunosorbent assay and single-antigen bead assays. Donor-specific cytotoxic potential was tested by standard CDC cross-match analysis. The presence of donor-specific or total HLA antibodies was not predictive for the occurrence of acute rejection after the reduction of immunosuppression. In addition, the presence of HLA antibodies did not preclude successful reduction of immunosuppression. After reduction of immunosuppression, newly formed HLA antibodies were seldom detected. Interestingly, evaluation of the cytotoxic potential of the detected HLA antibodies revealed that the one patient who developed donor-specific HLA antibodies and experienced a subsequent rejection episode was the only patient who carried cytotoxic HLA antibodies. This finding fueled the notion that the functional capacity, rather than the mere presence of donor-specific HLA antibodies, is indicative for transplant outcome. The presence of HLA antibodies does not preclude the successful reduction of immunosuppression in renal transplant patients with stable graft function.