Clinical Transplant Centers Core

临床移植中心核心将由10个主要的学术移植中心组成， 美国每年大约进行1360例成人肾脏移植手术。其活动 将通过临床数据库与三个科学项目相结合， 项目网站、年度科学会议和10个临床研究中心之间的积极中期互动 研究者和主要研究者。本核心的重点目标是为项目提供必要的患者材料和相关临床数据，以测试以下假设： 1)PBL和肾移植活组织检查中的基因表达和蛋白质组特征可以 确定与活检证实的急性排斥反应和慢性移植物肾病相关，2） 基因和蛋白质表达谱将提供对宿主免疫应答和供体器官对移植的应答中所涉及的分子途径的了解，3）通过基因和蛋白质表达谱可以在任何给定时间确定免疫抑制的充分性，所述免疫抑制的充分性由不存在排斥相关基因和蛋白质表达所定义，和4）靶向SNP基因分型和候选基因序列研究将鉴定供体和受体的遗传学之间的联系，其与移植事件和结果以及与基因和蛋白质表达标记相关。在所有这些假设的基础上，我们建议研究种族（高加索人，非洲裔美国人和西班牙裔）和/或性别对移植后表达的基因和蛋白质的至少一个子集产生遗传影响并与临床结果相关的可能性。一个关键点是，患者亚组的正确临床指定以及成功完成入组和标本采集（本核心的两项主要任务）将决定整个计划项目中所有科学家的成功潜力。

The Clinical Transplant Center Core will be comprised of 10 major academic transplant centers in the United States doing approximately 1360 adult kidney transplants per year in total. Its activities will be integrated with the three Scientific Projects through the Clinical Database, the Program Project website, yearly scientific meetings and active interim interactions between the 10 Clinical Investigators and the Principal Investigators. Our focused objectives for this Core are to provide the Projects with the requisite patient materials and correlating clinical data to test the hypotheses that: 1) gene expression and proteomic signatures in PBL and kidney transplant biopsies can be identified that correlate with biopsy-proven acute rejection and chronic allograft nephropathy, 2) gene and protein expression profiles will provide insights into the molecular pathways involved in both the host immune response and the donor organ's response to transplantation, 3) the adequacy of immunosuppression as defined by the absence of rejection-related gene and protein expression can be determined at any given time by gene and protein expression profiles, and 4) targeted SNP genotyping and candidate gene sequence studies will identify connections between the genetics of the donor and the recipients that correlate with transplant events and outcomes as well as with gene and protein expression signatures. Arching over all these hypotheses, we propose to examine the possibility that race (Caucasian, African American and Hispanic) and/or sex will genetically influence at least a subset of genes and proteins expressed post transplant and correlate with clinical outcomes. A critical point is that the correct clinical designations of the patient subgroups and successful completion of enrollment and specimen acquisitions, the two primary tasks for this Core, will determine the potential of success for all the scientists in the entire Program Project.