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

肾移植患者 CMV 和 BK 病毒免疫的纵向评估

基本信息

批准号：
8650259
负责人：
DAVID MARTIN MURDOCH
金额：
$ 19.63万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-15 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8650259
关键词：
Acute Adoption Adverse effects Antibodies Antigens Antithymoglobulin Antiviral Therapy BK Virus Benefits and Risks Biological Assay CD4 Antigens CD8B1 gene Candida Candida albicans Cellular Assay Cellular Immunity Chemoprophylaxis Chronic Clinical Communicable Diseases Cytomegalovirus Data Development Disease Ensure Epitopes Equilibrium Flow Cytometry Graft Survival Health Hematopoietic stem cells Hypersensitivity skin testing Immune Immune response Immunity Immunologic Monitoring Immunology Immunosuppression Immunosuppressive Agents Individual Infection Interleukin-2 Intervention Investigation Kidney Diseases Kidney Transplantation Knowledge Maintenance Measurement Measures Monitor Nonparametric Statistics Opportunistic Infections Organ Transplantation Outcome Pathogenesis Patients Pattern Peptides Pharmaceutical Preparations Phenotype Polyomavirus Population Prophylactic treatment Regimen Regulatory T-Lymphocyte Reporting Research Risk Role Self Tolerance Solid Specimen Staging Stem cell transplant T cell response T-Cell Depletion T-Lymphocyte T-Lymphocyte Subsets Techniques Time Titrations Translations Transplant Recipients Transplantation Valganciclovir Viremia allograft rejection base basiliximab chemotherapy clinical care clinical practice design disorder risk early onset graft vs host disease immunosuppressed improved kidney infection late disease onset prophylactic reconstitution repository response tool transplantation medicine viral DNA

项目摘要

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

描述（由申请人提供）：该提案概述了肾移植受者中BK病毒（BKV）免疫发病发生的两年研究计划。肾移植医学的主要临床障碍是由于BKV引起的多瘤病毒相关肾病（PVAN）的发生，在移植物后期，BK病毒血症（13％）和PVAN（8％）的出现显着出现。最佳免疫抑制以确保移植物生存率必须与感染风险保持平衡。抗体水平是疾病风险或对抗病毒疗法反应的预测因素，基于病毒DNA PCR的测定没有直接提供有关免疫状态的信息。但是，目前尚无细胞免疫监测测定法，用于肾移植受者的临床用途。 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）。肾移植后，我们将对120名患者进行纵向免疫监测（第0、4、12、24和48周）。由于很少这样的PFC分析报告这种抗原特异性T细胞反应的鲁棒测量，因此我们将在早期（0-3个月）和后期（6-12个月）转移后期（6-12个月）在免疫重建后期（0-3个月）和晚期（6-12个月）进行客观地量化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，我们最终旨在填补科学知识和临床实践的空白，以单独滴定免疫抑制和化学预防性方案，以改善移植临床护理和结果