Immune Parameters in a Steroid Sparing Clinical Trial

描述(由申请人提供)：在选定的低风险受者中进行了类固醇停用的研究，以减少类固醇移植后的许多副作用，但与急性排斥反应的发生率增加有关。最近，类固醇避免免疫抑制方案已经实施。短期结果表明，急性排斥反应的发生率没有增加；然而，这些方案对移植物功能和存活率的长期影响尚不清楚。目前在明尼苏达大学进行的快速停用强的松的三臂临床试验旨在确定最佳的长期类固醇避免免疫抑制方案。需要免疫参数来研究急性和慢性排斥的机制，并确定是否可以预测移植的短期和长期结果。理想情况下，这些免疫参数可以识别急性、亚急性和慢性排斥反应的高危受体。我们的目标是确定移植前和移植后对供者抗原反应的测量是否可以预测移植结果，从而允许个体化免疫抑制并确定潜在的干预点。第一个专门的目的是研究与急性排斥反应有关的免疫机制，使用旨在确定供者抗原特异性免疫参数(包括ELISpot、细胞内ATP合成和低水平抗-HLA抗体)是否可以识别出发生急性和亚临床排斥反应的高风险受体的方法。第二个具体目的是研究与慢性排斥反应相关的免疫机制，概述了检测ELISpot中供体抗原特异性直接和间接识别供体抗原/肽的分析方法，以及流式细胞仪分析方法是否可以识别出发生慢性排斥反应的高风险受体。第三个特定目标的研究旨在确定细胞内ATP合成的测量是否可以准确地测量在联合免疫抑制试剂存在的情况下的免疫反应，并可以预测过度免疫抑制。这些研究对于迅速提醒临床医生注意免疫状态的任何变化和对三种免疫抑制方案的总体反应都是重要的。因此，整个研究的目的是使用免疫参数来识别移植物预后不良的低风险和高风险的受者，从而允许个体化免疫抑制，旨在改善长期移植物预后。

DESCRIPTION (provided by applicant): 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.