Immune Parameters in a Steroid Sparing Clinical Trial

描述（由申请人提供）：在选定的低风险受体中进行类固醇停药研究，以减少类固醇移植后的许多副作用，但与急性排斥反应率增加有关。最近，类固醇回避免疫抑制方案已经实施。短期结果显示急性排斥反应率没有增加；然而，这些方案对移植物功能和存活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泼尼松的三组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反应的机制，并确定短期和长期移植结果是否可以预测。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高风险的受体。我们的目标是确定是否测量移植前和移植后对供体抗原的反应可以预测移植结果，从而允许免疫抑制的个体化和确定潜在的干预点。第一个特定目的是研究急性排斥反应的免疫机制，使用旨在确定供体抗原特异性免疫参数（包括ELISpot，细胞内ATP合成和低水平的抗hla抗体）是否可以识别急性和亚临床排斥反应高风险的受体。第二个特定目标，旨在研究与慢性排斥反应相关的免疫机制，概述了检测供体抗原特异性直接和间接识别供体抗原/肽的ELISpot和流式细胞术检测是否可以识别发生慢性排斥反应的高风险受体的检测方法。第三个特异性目的的研究旨在确定细胞内ATP合成的测量是否能准确测量联合免疫抑制试剂存在下的免疫反应，并能预测过度免疫抑制。这些研究对于迅速提醒临床医生免疫状态的任何变化和对三种免疫抑制方案的总体反应是重要的。因此，整个研究的目的是使用免疫参数来识别移植预后不良的低风险和高风险受体，从而允许个体化免疫抑制，以改善长期移植预后。

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.