URINARY CELL MRNA PROFILES OF REJECTION

尿细胞 mRNA 排斥谱

• 批准号: 7604152
• 负责人: Darshana Dadhania
• 金额: $ 1.71万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604152
• 关键词: Acute; Allografting; Biological Assay; CD3 Antigens; Cells; Clinical; Computer Retrieval of Information on Scientific Projects Database; Country; Creatinine; Data; Deterioration; Diagnosis; Diagnostic; Equation; Failure; Funding; Grant; Immune response; Immunosuppression; Institution; Kidney Transplantation; Maintenance; Measurement; Measures; Messenger RNA; Molecular Profiling; Multicenter Trials; Organ Donor; Polymerase Chain Reaction; Renal function; Research; Research Personnel; Resources; Risk; Risk Factors; Sensitivity and Specificity; Serum; Source; Specificity; Surrogate Markers; Testing; Therapeutic immunosuppression; Time; Transplantation; United States National Institutes of Health; granzyme B; kidney allograft; noninvasive diagnosis; perforin; prospective; urinary

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Clinical acute rejection, defined as a sudden deterioration in renal-allograft function as a result of the recipient's immune response to the donor organ, is a major risk factor for allograft failure. An increase in the serum creatinine level is often the first clinical indicator, and currently the best surrogate marker of acute rejection. This marker lacks sensitivity and specificity. We will test the hypothesis that urinary cell mRNA profiles identify allografts at risk for progressive decline in renal function. Urinary cell mRNA profiling will be performed at pre-defined time points in year one of transplantation. Renal function will be assessed by measuring serum creatinine levels at 12, 24, and 36 months following renal transplantation and estimating GFR with MDRD equation. We are proposing to measure levels of mRNA for perforin, granzyme B and CD3 in urinary cells obtained during the first 12 months after transplantation. Our recent studies suggest that noninvasive diagnosis of acute rejection of renal allografts is feasible by measurement of mRNA for perforin, granzyme B, and CD3 with a specificity of 95% and sensitivity of 95%. Data must be validated in a prospective multicenter trial prior to its application as a routine assay in the clinical setting. The study will demonstrate whether this molecular profiling is predictive and diagnostic, reliable and portable for all transplant centers in the country; whether urinary PCR profile can prognosticate and/or diagnose the occurrence of acute rejection; and whether the results are independent of the type of induction and maintenance immunosuppression.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 临床急性排斥反应，定义为由于受体对供体器官的免疫反应而导致的肾移植物功能的突然恶化，是同种异体移植物失败的主要危险因素。血清肌酐水平的增加通常是第一个临床指标，目前是急性排斥反应的最佳替代标志物。该标志物缺乏敏感性和特异性。我们将检验尿细胞mRNA谱识别肾功能进行性下降风险的同种异体移植物的假设。将在移植第一年的预定时间点进行尿细胞mRNA分析。将通过测量肾移植后12、24和36个月的血清肌酐水平并使用MDRD方程估计GFR来评估肾功能。我们建议在移植后的前12个月内测量尿细胞中穿孔素、颗粒酶B和CD 3的mRNA水平。我们最近的研究表明，通过检测穿孔素、颗粒酶B和CD 3的mRNA，无创性诊断移植肾急性排斥反应是可行的，特异性为95%，敏感性为95%。数据必须在前瞻性多中心试验中进行验证，然后才能作为临床环境中的常规检测方法应用。该研究将证明这种分子谱是否具有预测性和诊断性，可靠性和便携性，适用于该国所有移植中心;尿PCR谱是否可以预测和/或诊断急性排斥反应的发生;以及结果是否独立于诱导和维持免疫抑制的类型。