Studies of steroid withdrawal in selected low-risk recipients have been implemented to decrease the numerous post transplant side effects of steroids but have been associated with an increased rate of acute rejection. More recently, steroid avoidance immunosuppression protocols have been implemented. The short-term results show there is no increase in the rate of acute rejection; however, the long-term effects of these protocols on graft function and survival are not known. The current three-arm clinical trial of rapid discontinuation of prednisone at the University of Minnesota is designed to determine the best long-term steroid avoidance immunosuppressive protocol. Immune parameters are needed to investigate mechanisms of acute and chronic rejection and to determine if short- and long-term graft outcome can be predicted. Ideally, these immune parameters could identify recipients at high risk for acute, subacute, and chronic rejection. Our goal is to determine if measurement of pre- and post transplant responses to donor antigen can predict graft outcome, thereby allowing for individualization of immunosuppression and identifying potential points for intervention. The first specific aim is focused on investigating immune mechanisms involved in acute rejection using assays designed to determine if donor antigen-specific immune parameters, including ELISpot, intracellular ATP synthesis, and low levels of anti-HLA antibody can identify recipients at high risk for developing acute and sub-clinical rejection. The second specific aim, designed to study immune mechanisms associated with chronic rejection, outlines assays which test if donor antigen-specific direct and indirect recognition of donor antigen/peptides in ELISpot and flow cytometric assays can identify recipients at high risk for developing chronic rejection. Studies of the third specific aim are designed to determine if the measurement of intracellular ATP synthesis can accurately measure the immune response in the presence of the combined immunosuppressive reagents and can predict over-immunosuppression. These studies are important to quickly alert clinicians to any changes in immune status and overall response to the three immunosuppression regimes. Thus, the overall study is designed to use immune parameters to identify recipients at low vs. high risk for poor graft outcome, thereby allowing for individualization of immunosuppression aimed at improving long-term graft outcome.
| Reinsmoen, Nancy L; Cornett, Karen M M; Kloehn, Robert et al. (2008) Pretransplant donor-specific and non-specific immune parameters associated with early acute rejection. Transplantation 85:462-70 |
