IMMUNE PARAMETERS ACCOMPANYING LONG TERM GRAFT SUCCESS

在大多数移植计划中，长期接受移植的人往往 接受类似的免疫抑制方案治疗。然而，这样的 统一治疗可能会导致过度免疫抑制的并发症 一些是免疫抑制不足，另一些是免疫抑制不足。以前的研究 一种免疫抑制药物的停用尚未成功。一个 重要的问题是，个人免疫参数检测或 一系列这些测试将最好地预测移植的长期结果 病情稳定的病人。来自各个实验室的回溯数据 提示免疫参数(供体抗原特异性低反应性 和同种异体微嵌合体)预测成功的长期结果 在实体器官移植后。但是，这些参数中的每个参数 仅适用于移植受者的一小部分。这 格兰特将专注于这两种免疫学的潜在用途 广泛移植中预测长期移植物成功的参数 人口。我们将确定捐赠者的抗原特异性 辅助途径的低反应性(特定目标1)，以及外周 血液同种异体微嵌合体(特定目标2)，与 改善了移植物的长期结果。我们将进行一项前瞻性研究， 检测肝脏和肾脏受者的这两个免疫参数 移植到杜克大学医学中心和华盛顿大学 明尼苏达州。两所大学都有长期建立的机制 临床随访和临床资料收集。我们将评估 这些免疫参数在每个器官组中的有用性。我们会 确定，也许在特定器官组中，一个参数是否可以 被用来代替另一个。同时，我们的多中心方法 将允许我们测试大量收件人；我们将能够 积累关于足够数量的收件人的数据以测试空值 假设。成功，我们随后计划使用这些免疫力 确定免疫抑制是否可以个体化的参数。如果 因此，通过选择性地降低一些受者的免疫抑制，但 在其他地方保持它，我们将提供大量的长期节省 实体器官移植的成本、发病率和结果改善 收件人。

In most transplant programs, long-term transplant recipients tend to be treated with similar immunosuppressive protocols. However, such uniform treatment may lead to complications from overimmunosuppression in some and underimmunosuppression in others. Previous studies of withdrawal of one immunosuppressive drug have not been successful. An important question is whether an individual immune parameter test or a battery of these tests would best predict long-term graft outcome in stable patients. Retrospective data from individual laboratories has suggested that immune parameters (donor antigen-specific hyporeactivity and allogeneic microchimerism) predict successful long-term outcome after solid organ transplantation. However, each of these parameters has only been applied to a subpopulation of transplant recipients. This grant will focus on the potential use of these two immunologic parameters to predict long-term graft success in a broad transplant population. We will determine whether donor antigen-specific hyporeactivity o the helper pathway (Specific Aim 1), and peripheral blood allogeneic microchimerism (Specific Aim 2), correlate with improved long-term graft outcome. We will perform a prospective study, testing these two immune parameters for, liver and kidney recipients transplanted at Duke University Medical Center and University of Minnesota. Both universities have long-established mechanisms for clinical follow-up and clinical data collection. We will evaluate the usefulness of these immune parameters in each organ group. We will determine whether, perhaps in specific organ groups one parameter can be used in lieu of another. At the same time our multicenter approach will allow us to test large numbers of recipients; we will be able to accumulate data on sufficient numbers of recipients to test the null hypothesis. successful, we subsequently plan to use these immune parameters to determine if immunosuppression can be individualized. If so, by selectively lowering immunosuppression in some recipients but maintaining it in others, we will provide significant long-term savings (cost, morbidity, and outcome improvement) for solid organ transplant recipients.