IMMUNE PARAMETERS ACCOMPANYING LONG TERM GRAFT SUCCESS

伴随长期移植成功的免疫参数

• 批准号: 2660426
• 负责人: Nancy Louise Reinsmoen
• 金额: $ 25.52万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2660426
• 关键词: antibody specificity; artificial immunosuppression; clinical research; data collection methodology /evaluation; histocompatibility antigens; human subject; immune complex; kidney transplantation; liver transplantation; longitudinal human study; 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 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.

在大多数移植项目中，长期移植受者往往 接受类似的免疫抑制治疗但这种 统一的治疗可能会导致过度免疫抑制的并发症 在一些人中，而在另一些人中，免疫抑制不足。以往的研究 一种免疫抑制药物的撤药尚未成功。一个 重要问题是个体免疫参数测试或 一组这些测试将最好地预测长期移植结果， 稳定的患者。来自各个实验室的回顾性数据 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。然而，这些参数中的每一个 只适用于移植受者的亚群。这 格兰特将重点关注这两种免疫学的潜在用途， 在广泛移植中预测长期移植成功的参数 人口我们将确定供体抗原特异性 辅助通路（特异性Aim 1）的低反应性，以及外周 血液同种异体微嵌合体（特异性目的2），与 改善移植物的长期结局。我们将进行一项前瞻性研究， 测试这两个免疫参数，肝脏和肾脏受体 移植在杜克大学医学中心和 明尼苏达两所大学都有长期建立的机制， 临床随访和临床数据收集。我们将评估 这些免疫参数在每个器官组中的有用性。我们将 确定是否，也许在特定的器官组中，一个参数可以 代替另一个。同时，我们的多中心方法 将允许我们测试大量的接受者;我们将能够 积累足够数量的接收者的数据来测试空值 假说.成功后，我们计划使用这些免疫 参数，以确定免疫抑制是否可以个体化。如果 因此，通过选择性地降低某些受体的免疫抑制， 在其他方面保持这一点，我们将提供大量的长期储蓄， (cost、发病率和结果改善）用于实体器官移植 受惠人士

项目成果

Cytokine genotypes in kidney, heart, and lung recipients: consequences for acute and chronic rejection.

肾脏、心脏和肺受体的细胞因子基因型：急性和慢性排斥反应的后果。

• DOI: 10.1016/s0041-1345(00)02106-0
• 发表时间: 2001
• 期刊: Transplantation proceedings
• 影响因子: 0.9
• 作者: Jackson,A;Palmer,S;Davis,RD;Pappendick,A;Pearson,E;Savik,K;Ormaza,S;Hertz,M;Dacey,M;Miller,L;Reinsmoen,NL
• 通讯作者: Reinsmoen,NL