CORRELATION OF IMMUNE PARAMETERS WITH OUTCOME

免疫参数与结果的相关性

• 批准号: 6448969
• 负责人: Nancy Louise Reinsmoen
• 金额: $ 18.5万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6448969
• 关键词: antibody formation; artificial immunosuppression; clinical research; heart transplantation; helper T lymphocyte; histocompatibility antigens; human subject; human therapy evaluation; immunologic assay /test; isoantibody; kidney transplantation; lung transplantation; outcomes research; transplant rejection; transplantation immunology

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 over immunosuppression in some and under immunosuppression in others. Previous studies of withdrawal of one 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 the immune parameters (donor antigen-specific hyporeactivity, allogeneic microchimerism, and the absence of donor antigen-specific HLA antibodies) predict successful long- term outcome after solid organ transplantation. However, each of these parameters has only been applied individuals and only to a subpopulation of transplant recipients. This grant will focus on the use of these three immunologic parameters to predict long-term graft success in a broad transplant population. We will determine whether donor antigen-specific hyporeactivity of the CD4 helped pathway (Specific Aim 1), peripheral blood allogeneic microchimerism (Specific Aim 2), and a lack of development (or regulation of) donor antigen-specific HLA antibodies (Specific Aim 3) correlate with improved long-term graft outcome. We will perform a prospective study, testing all three parameters for lung and heart recipients and the first and third parameters for kidney recipients transplant at the University of Minnesota. The transplant program at the University of Minnesota has a long-established mechanisms for clinical follow-up and clinical data collection. We will determine whether one parameter can be used in lieu of another in an organ specific manner. We plan to use these immune parameters to determine if immunosuppression can be individualized, If so, by selectively lowing immunosuppression in some recipient by maintaining it in others, we will provide significant long- term savings (cost, morbidity and outcome improvement) for solid organ transplant recipients.

在大多数移植计划中，长期接受移植的人往往是 用类似的免疫抑制方案治疗。然而，这样的制服 在某些情况下，治疗可能会导致过度免疫抑制的并发症 另一些则处于免疫抑制状态。前人对戒断行为的研究 有一种药物没有成功。一个重要的问题是，一个 单独的免疫参数测试或一系列这样的测试是最好的 预测稳定患者的长期移植结果。回溯数据 来自个别实验室的研究表明，免疫参数(捐赠者 抗原特异性低反应性、同种异体微嵌合体和 缺乏供者抗原特异性的人类白细胞抗原抗体)预测长期移植的成功 实体器官移植后的远期结局。然而，这其中的每一个 参数仅应用于个体且仅应用于子群体 移植受者的数量。这笔拨款将集中在使用这三个方面 免疫学参数在广泛预测移植长期成功中的作用 移植人口。我们将确定捐赠者的抗原特异性 外周CD4辅助途径的低反应性(特异靶1) 血液同种异体微嵌合体(特定目标2)，以及缺乏 开发(或调节)供体抗原特异性的人类白细胞抗原抗体 (特定目标3)与改善长期移植结果相关。我们会 进行前瞻性研究，测试所有三个参数的肺和 心脏移植受者和肾移植受者的第一和第三参数 移植到明尼苏达大学。该中心的移植计划 明尼苏达大学有着悠久的临床机制 随访及临床资料收集。我们将确定是否会有一个 参数可以器官特定的方式用来代替另一个参数。我们 计划使用这些免疫参数来确定免疫抑制是否可以 如果是这样的话，通过选择性地降低某些患者的免疫抑制，使其个体化 通过在其他人身上保持这一点，我们将提供重要的长期- 实体器官的长期节省(成本、发病率和结果改善) 移植受者。