Stromal Gene Expression During Pulmonary Sarcoidosis

描述（由申请人提供）： 结节病是一种原因不明的疾病，仅在美国就有数万名患者受到折磨。该疾病的表现是高度可变的，从临床上难以察觉的疾病到由肺和/或其他重要器官中的广泛肉芽肿形成引起的危及生命的并发症。许多结节病病例是散发性的，而另一些病例在家庭和种族群体中聚集，这意味着疾病的遗传偏好。 最近的调查支持遗传变量和结节病之间的联系。例如，与调节炎症的起始和持续的基因非常接近的核苷酸多态性与结节病密切相关。然而，全基因组突变分析的分辨率较低，可能会遗漏许多可能导致疾病发病机制的基因，同时识别其他不相关的基因。相比之下，DNA表达分析具有相对高的分辨率（> 12，000个基因），可以在组织样品上进行，以提供疾病活动部位的基因表达模式，以及基因过度表达和表达不足方面的定量反馈。因此，可能促进疾病的基因可以与调节疾病活性的基因区分开。因此，本提案将分析结节病患者病变组织中的基因表达模式，以实现以下目标：目标1：鉴定与活动性肺结节病特异性相关的基因表达模式。目的2：确定基因表达模式是否与结节病患者的疾病严重程度相关。目的3：确定基因表达模式是否能区分结节病引起的肉芽肿和组织胞浆菌病引起的肉芽肿。基因表达模式将由来自新诊断的结节病成人组织样本、匹配的正常组织和组织胞浆菌病患者组织的总RNA生成，组织胞浆菌病是一种临床上与结节病相似的肉芽肿性疾病。然后将进行基因表达模式的统计比较。新的见解基因谱与疾病的表现，预后和发病机制可能是这些调查的结果。

DESCRIPTION (provided by applicant): Sarcoidosis is a disease of unknown cause afflicting tens of thousands of patients in the USA alone. The presentation of the disease is highly variable, ranging from clinically imperceptible disease to life-threatening complications caused by extensive granuloma formation in the lungs and/or other vital organs. Many cases of sarcoidosis are sporadic, while others cluster within families and racial groups, implying a genetic predilection for disease. Recent investigations support a link between genetic variables and sarcoidosis. For instance, nucleotide polymorphisms in close proximity to genes regulating the initiation and perpetuation of inflammation are strongly associated with sarcoidosis. However, genome-wide mutation analyses are of low resolution, potentially missing many genes that may contribute to disease pathogenesis, while identifying others that are irrelevant. By contrast, DNA expression analyses are of relatively high resolution (>12,000 genes), can be performed on tissue samples to provide gene expression patterns at the site of disease activity, and quantitative feedback in terms of gene over- and under-expression. As such, genes that are likely to promote disease may be distinguished from those that modulate disease activity. Therefore, this proposal will analyze gene expression patterns in diseased tissues of patients with sarcoidosis to accomplish the following aims: Aim 1: To Identify Gene Expression Patterns That Specifically Correlate with Active Pulmonary Sarcoidosis. Aim 2: To Determine If Gene Expression Patterns Correlate With The Severity of Illness Of Sarcoidosis Patients. Aim 3: To Determine If Gene Expression Patterns Will Differentiate Granuloma Caused By Sarcoidosis From Those Caused by Histoplasmosis. Gene expression patterns will be generated from total RNA derived from tissue samples of adults with newly diagnosed sarcoidosis, matching normal tissue, and tissues of patients with histoplasmosis, a granulomatous disease that is clinically similar to sarcoidosis. Statistical comparisons of gene expression patterns will then be performed. Novel insights relating gene profiles to disease manifestation, prognosis and pathogenesis are likely outcomes of these investigations.