Characterizing Uveitis by Gene Expression

通过基因表达表征葡萄膜炎

• 批准号: 9235011
• 负责人: JAMES T ROSENBAUM
• 金额: $ 38.5万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9235011
• 关键词: Acquired Blindness; Acute; Affect; Ankylosing spondylitis; Anterior uveitis; Behcet Syndrome; Big Data; Blindness; Blood; Categories; Classification; Clinical; Data; Diabetes Mellitus; Diagnosis; Diagnostic; Differential Diagnosis; Disease; Emerging Technologies; Etiology; Eye; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genes; Immune; Infection; Inflammation; Inflammatory Bowel Diseases; Label; Lymphoma; Macular degeneration; Mediating; Molecular Profiling; Morbidity - disease rate; Movement; Patients; Pharmaceutical Preparations; Physicians; Process; RNA; Sarcoidosis; Sensitivity and Specificity; Series; Spondylarthritis; Study Subject; Syndrome; Systemic disease; Technology; Testing; Therapeutic; Time; Transcript; Tubulointerstitial Nephritis; Uveitis; Visual; clinical phenotype; disease phenotype; patient subsets; peripheral blood; precision medicine; prognostic; retinochoroidopathy; success; tool; transcriptome; transcriptome sequencing

Project Summary Uveitis accounts for as much acquired visual loss as diabetes or macular degeneration. Although many entities cause uveitis, the most frequent diagnosis is “idiopathic”, a description that frustrates patients and physicians. We have shown that some systemic diseases associated with uveitis demonstrate distinct gene expression profiles that can be identified in blood. We propose to characterize the gene expression profile for 4 important causes of uveitis: sarcoidosis, ankylosing spondylitis, inflammatory bowel disease, and tubulointerstitial nephritis with uveitis. Our study will determine if the profiles for each disease have adequate sensitivity and specificity to become diagnostic tools. We will test the hypothesis that many diseases that cause uveitis share expression of common RNA transcripts. We will segregate subjects with idiopathic uveitis on the basis of gene expression and validate this classification by determining if the clinical phenotype of the uveitis fits with the gene expression profile. By studying subjects longitudinally over the course of the proposal, we will distinguish transcripts that are indicative of the disease phenotype in contrast to transcripts that are indicative of the disease activity. The proposed studies represent a potential paradigm shift in the approach to uveitis and a prime example of the application of precision medicine to a clinical conundrum.

项目摘要 葡萄膜炎造成的获得性视力损失与糖尿病或黄斑变性一样多。 虽然许多实体会引起葡萄膜炎，但最常见的诊断是“特发性”，这是一种描述 这让患者和医生感到沮丧。我们已经证明了一些系统性疾病 与葡萄膜炎相关的表现出独特的基因表达谱，可以在 血。我们建议对葡萄膜炎的四个重要原因的基因表达谱进行表征： 结节病、强直性脊柱炎、炎症性肠病和肾小管间质性肾炎 葡萄膜炎。我们的研究将确定每种疾病的特征是否具有足够的敏感性 和特异性成为诊断工具。我们将检验这样一种假设，即许多疾病 引起葡萄膜炎共表达常见的RNA转录本。我们将通过以下方式分隔受试者 基于基因表达的特发性葡萄膜炎，并通过确定 葡萄膜炎的临床表型是否符合基因表达谱。通过研究科目 在提案的纵向过程中，我们将区分以下文字记录 疾病表型与指示疾病活动性的转录本形成对比。这个 拟议的研究代表了葡萄膜炎治疗方法的潜在范式转变和主要的 精准医学应用于临床难题的例子。