Defining Biomarkers in Pediatric Renal Transplantation

定义小儿肾移植中的生物标志物

• 批准号: 7067580
• 负责人: Minnie M Sarwal
• 金额: $ 39.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067580
• 关键词: biomarker; case history; clinical research; diagnosis design /evaluation; disease /disorder proneness /risk; gene expression; human subject; immunocytochemistry; immunopathology diagnosis; immunosuppression; kidney transplantation; microarray technology; noninvasive diagnosis; patient oriented research; pediatrics; polymerase chain reaction; tissue /cell preparation; transplant rejection

DESCRIPTION (provided by applicant): We propose to undertake a comprehensive mechanistic study to establish informative biomarkers in pediatric renal transplantation, using patient clinical data and tissue (biopsy and blood) from SNS01- a randomized clinical trial of steroid-free versus steroid-based immunosuppression. This proposal outlines a strategy for integrating clinical and pathology cores from SNS01 with genomic (cDNA arrays and real-time PCR) and immunopathology (core biopsies and tissue microarrays) cores, the latter two cores to be generated by this proposal. The aims of this study are fourfold. (i) To develop diagnostic biomarkers by DNA microarray analysis, in tissue and blood for stable transplants, acute rejection (AR) and chronic allograft nephropathy (CAN). (ii) To detect differences in these graft states in steroid-free and steroid-based immunosuppression. (iii)To correlate the expression of selected highly differentiated genes in tissue and blood, using real-time PCR, to establish non-invasive blood markers for graft surveillance, AR diagnosis, classification, and stratification of AR therapy and outcome. (iv) To use immunohistochemistry analysis on core patient biopsies and tissue microarrays to correlate gene expression data with cellular infiltration phenotypes, density and activation in AR, CAN and normal post-transplant kidneys, in steroid-free and steroid-based immunosuppression. These studies are expected to facilitate the definition of immunological and cellular mechanisms underlying stable transplants and different forms of renal allograft dysfunction, different types of immunosuppression (with and without steroids), and generate clinical tools for non-invasive graft monitoring, as well as graft therapeutic and risk stratification. The genomic and tissue microarray databases will be made publicly available for the academic community to facilitate future large-scale collaborative studies.

描述（由申请人提供）：我们建议开展一项全面的机制研究，利用患者临床数据和来自SNS01的组织（活检和血液），建立儿童肾移植的信息性生物标志物。SNS01是一项无类固醇与基于类固醇的免疫抑制的随机临床试验。本提案概述了将SNS01的临床和病理核心与基因组（cDNA阵列和实时PCR）和免疫病理（核心活检和组织微阵列）核心整合的策略，后两个核心将由本提案生成。这项研究的目的有四个方面。(i)通过DNA微阵列分析，在组织和血液中开发用于稳定移植、急性排斥反应（AR）和慢性同种异体移植肾病（CAN）的诊断性生物标志物。（ii）检测无类固醇和基于类固醇的免疫抑制在这些移植物状态中的差异。（iii）利用实时荧光定量PCR技术将组织和血液中选定的高度分化基因的表达联系起来，建立无创血液标志物，用于移植物监测、AR诊断、分类、AR治疗和结果分层。（iv）在无类固醇和基于类固醇的免疫抑制中，对核心患者活检和组织微阵列进行免疫组织化学分析，将基因表达数据与AR、CAN和正常移植后肾脏的细胞浸润表型、密度和激活联系起来。这些研究有望促进对稳定移植和不同形式的同种异体肾移植功能障碍、不同类型的免疫抑制（有和没有类固醇）的免疫和细胞机制的定义，并为无创移植监测以及移植治疗和风险分层提供临床工具。基因组和组织微阵列数据库将向学术界公开，以促进未来的大规模合作研究。