Proteomics of Kidney Transplantation

肾移植的蛋白质组学

• 批准号: 7280808
• 负责人: John R Yates III
• 金额: $ 25.26万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7280808
• 关键词: artificial immunosuppression; biopsy; biotechnology; cooperative study; functional /structural genomics; human subject; kidney disorder; kidney transplantation; liquid chromatography mass spectrometry; longitudinal human study; lymphocyte; patient oriented research; protein quantitation /detection; proteomics; statistics /biometry; transplant rejection; transplantation immunology

Kidney transplantation has extended and improved the quality of life for many patients with end stage renal disease. Most transplants involve genetically non-identical donor to recipient combinations. As a consequence the immune response is a major impediment to successful graft survival, necessitating life-long treatment with potent immunosuppressive drugs. The donor organ and its complex responses to transplantation is also a major player in all the events determining the clinical events post transplant. Despite recent reductions in the incidence of acute rejection, chronic rejection and immunosuppressive drug side effects are still major causes of graft loss and patient morbidity. In this context, it is essential to advance our understanding of the immune response and the responses of the transplanted organ to both immune and non-immune injury mechanisms. We will use quantitative shotgun proteomics based on liquid chromatography tandem mass spectrometery to identify protein expression changes in transplanted kidneys and peripheral blood lymphocytes. Proteins will be identified and their expression levels measured relative to samples from patients with well-functioning transplants and no history of rejection. The objectives will be to identify regulatory processes activated or suppressed as a result of the immune response and identify cellular pathways associated with immunity, cell injury and tissue repair. Proteomics data will be integrated with gene expression measurements to gain a more complete view of the rejection process for both protein and gene transcript expression as well as identify and rank 500 gene candidates for complex trait genetics by SNP analysis.

肾移植延长并改善了许多终末期肾病患者的生活质量。大多数移植涉及遗传上不相同的供体与受体组合。因此，免疫反应是移植物成功存活的主要障碍，需要使用强效免疫抑制药物进行终生治疗。供体器官及其对移植的复杂反应也是决定移植后临床事件的所有事件的主要参与者。尽管最近急性排斥反应的发生率有所下降，但慢性排斥反应和免疫抑制药物副作用仍然是移植物丢失和患者发病的主要原因。在此背景下，有必要推进我们的 了解免疫反应以及移植器官对免疫和非免疫损伤机制的反应。我们将使用基于液相色谱串联质谱的定量鸟枪蛋白质组学来鉴定移植肾和外周血淋巴细胞中蛋白质表达的变化。相对于来自功能良好的移植物且无排斥史的患者的样本，将鉴定蛋白质并测量其表达水平。目标是确定由于免疫反应而激活或抑制的调节过程，并确定与免疫、细胞损伤和组织修复相关的细胞途径。蛋白质组学数据将与基因表达测量相结合，以获得蛋白质和蛋白质的排斥过程的更完整视图。 基因转录表达以及通过 SNP 分析识别和排序 500 个复杂性状遗传学候选基因。