cDNA Microarrays In Gene Expression Of Uveitis Patients

葡萄膜炎患者基因表达的 cDNA 微阵列

• 批准号: 6968560
• 负责人: ROBERT B. NUSSENBLATT
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 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/6968560
• 关键词: T lymphocyte; complementary DNA; gene expression; gene expression profiling; human tissue; immunogenetics; inflammation; leukocyte activation /transformation; microarray technology; serial analysis of gene expression; tumor necrosis factor alpha; uveitis

Ocular inflammatory diseases, including uveitis, cause significant visual loss. Previous non-human investigations have identified several cell types, receptor systems and metabolic intermediates that have led to treatment approaches for human patients. However,information on the human genetic expression of these steps in defined inflammatory disease states is lacking. This non-intervention study proposes to obtain peripheral blood and tissue specimens from patients enrolled in other intramural trials for ocular inflammatory diseases and to apply contemporary cDNA microarray technologies for the analysis of differential gene expression. Test results will not be reported to participants or used for diagnostic or therapeutic purposes.The study?s primary objective is to identify unique gene expression profiles as well as disease relevant genes for patients with ocular inflammatory disease at defined clinical stages using cDNA microarray analysis. This will help provide further insight to understand the pathological mechanisms and potential targets for treatment. Some 3,000-5,000 genes will be examined starting with a selected set associated with interleukin (IL) proteins and their receptors, and with tumor necrosis factors (TNF). Purified peripheral blood mononuclear cells (or whole blood lysates using RNA isolation procedures) will be used to isolate total RNA from these samples. Samples will be taken during periods of active or recurring inflammatory disease and again during periods of quiescence after treatment. The microarray tools and methods for genetic analysis are now available at the NEI.In conjunction with these studies are functional assays and cell surface markers of negative regulatory cells, so called ?suppressor cells?. These studies center for the moment on the CD25+ T cell fraction and certain markers of T cell activation such as GITR. A correlation is being made between T cell activation and these negative regulatory signals and clinical activity.

包括葡萄膜炎在内的眼部炎症性疾病会导致明显的视觉丧失。以前的非人类研究已经确定了几种细胞类型，受体系统和代谢中间体，这些细胞类型导致了针对人类患者的治疗方法。但是，缺乏有关这些步骤在定义的炎症性疾病状态下的人类遗传表达的信息。这项非干预研究提议从参加其他壁内试验的患者中获得外周血和组织标本，用于眼部炎症性疾病，并采用当代cDNA微阵列技术来分析差异基因表达。测试结果不会报告给参与者或用于诊断或治疗目的。该研究的主要目标是使用cDNA微阵列分析在定义的临床阶段确定独特的基因表达谱以及疾病相关的基因。这将有助于提供进一步的见解，以了解病理机制和潜在的治疗靶标。从与白介素（IL）蛋白及其受体相关的选定集以及与肿瘤坏死因子（TNF）相关的选定集开始，将检查约3,000-5,000个基因。纯化的外周血单核细胞（或使用RNA隔离程序的全血裂解物）将使用这些样品分离总RNA。样品将在活性或复发性炎症性疾病期间以及治疗后的静止期中再次采集。现在可以在NEI.结合使用这些研究的遗传分析的微阵列工具和方法，这是负调控细胞的功能测定和细胞表面标记，即称为“抑制细胞？”。这些研究中心在CD25+ T细胞分数和T细胞激活的某些标记（例如GITR）上中心。 T细胞激活与这些负调控信号和临床活性之间正在建立相关性。