Longitudinal assessment of CMV and BK virus immunity in renal transplant patients

描述（由申请人提供）：本提案概述了一项为期2年的肾移植受者BK病毒（BKV）免疫发病机制的调查研究计划。肾移植医学的一个主要临床障碍是由BKV引起的多瘤病毒相关性肾病（PVAN）的发生，在移植后期间，BK病毒血症（13%）和PVAN（8%）的发生率很高。确保移植物存活的最佳免疫抑制必须与感染风险相平衡。抗体水平不能很好地预测疾病风险或对抗病毒治疗的反应，基于病毒DNA pcr的检测不能提供有关免疫状态的直接信息。然而，目前还没有临床应用于肾移植受者的细胞免疫监测试验。为了填补这一空白，我们将使用四种高度优化的多色流式细胞术（PFC）检测来评估成熟亚群中的CD4和CD8 T细胞反应：CEF肽库（CD8反应的HLA I类限制性表位），假丝酵母CASTA （CD4活性），CMV pp65和e -1肽库（主要是CD8）和BKV肽库（CD4, CD8）。我们将对120例肾移植术后患者（第0、4、12、24和48周）进行纵向免疫监测。由于很少有这样的PFC检测报告这种抗原特异性T细胞反应的可靠测量，我们的目标是客观地量化移植后免疫重建早期（0-3个月）和晚期（6-12个月）的CD4/CD8 T细胞反应。通过客观和纵向量化抗原特异性免疫反应，我们的最终目标是填补科学知识和临床实践中的空白，为免疫抑制和化学预防方案的个体化滴定提供帮助，以改善移植临床护理和预后

DESCRIPTION (provided by applicant): This proposal outlines a 2-year plan for investigative research into the immunopathogenesis of BK virus (BKV) in renal transplant recipients. A major clinical barrier to renal transplant medicine is the occurrence of polyomavirus-associated nephropathy (PVAN) due to BKV, with significant occurrences of BK viremia (13%) and PVAN (8%) in the post-transplant period. Optimal immunosuppression to ensure graft survival must be balanced with infectious risk. Antibody levels are poor predictors of risk of disease or response to antiviral therapy and viral DNA PCR-based assays provide no direct information on the immune status. However, there are currently no cellular immune monitoring assays in clinical use for renal transplant recipients. To fill this gap, we will use four highly optimized polychromatic flow cytometry (PFC) assays designed to assess CD4 and CD8 T cell responses within maturational subsets: CEF peptide pool (HLA class I restricted epitopes for CD8 responses), Candida CASTA (CD4 activity), CMV pp65 & IE-1 peptide pools (primarily CD8) and BKV peptide pools (CD4, CD8). We will perform longitudinal immune monitoring in 120 patients following renal transplantation (weeks 0, 4, 12, 24, & 48). Because few such PFC assays report robust measurements of such antigen specific T cell responses, we will aim to objectively quantify CD4/CD8 T cell responses in the early (0-3 month) and late (6-12 month) post-transplant periods of immune reconstitution. By objectively and longitudinally quantifying antigen specific immune responses, we ultimately aim to fill gaps in scientific knowledge and clinical practice for the individual titration of immunosuppressive and chemoprophylaxis regimens to improve transplant clinical care and outcomes