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Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets

机译:外周血基因表达模式区分慢性炎症性疾病和健康对照,并确定新的靶标

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Background Chronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, but their pathogenesis is still not well understood. It is also not well known if distinct changes in gene expression characterize these diseases and if these patterns can discriminate between diseased and control patients and/or stratify the disease. The main focus of our work was the identification of novel markers that overlap among the 3 diseases or discriminate them from each other. Methods Diseased (n = 13, n = 15 and n = 12 in IBD, psoriasis and RA respectively) and healthy patients (n = 18) were recruited based on strict inclusion and exclusion criteria; peripheral blood samples were collected by clinicians (30 ml) in Venous Blood Vacuum Collection Tubes containing EDTA and peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. RNA was extracted using Trizol reagent. Gene expression data was obtained using TaqMan Low Density Array (TLDA) containing 96 genes that were selected by an algorithm and the statistical analyses were performed in Prism by using non-parametric Mann-Whitney U test (P-values Results Here we show that using a panel of 96 disease associated genes and measuring mRNA expression levels in peripheral blood derived mononuclear cells; we could identify disease-specific gene panels that separate each disease from healthy controls. In addition, a panel of five genes such as ADM, AQP9, CXCL2, IL10 and NAMPT discriminates between all samples from patients with chronic inflammation and healthy controls. We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition. Conclusions These findings and the identification of five universal markers of chronic inflammation suggest that these diseases have a common background in pathomechanism, but still can be separated by peripheral blood gene expression. Importantly, the identified genes can be associated with overlapping biological processes including changed inflammatory response. Gene panels based on such markers can play a major role in the development of personalized medicine, in monitoring disease progression and can lead to the identification of new potential drug targets in chronic inflammation.
机译:背景技术慢性炎性疾病包括炎性肠病(IBD;克罗恩病和溃疡性结肠炎),牛皮癣和类风湿关节炎(RA)困扰着全世界数百万人,但其发病机理仍未得到很好的了解。还不清楚基因表达的明显变化是否是这些疾病的特征,以及这些模式是否可以区分患病患者和对照患者和/或对疾病进行分层。我们工作的主要重点是鉴定在三种疾病之间重叠或彼此区分开的新标记。方法根据严格的纳入和排除标准,招募患病(IBD,牛皮癣和RA分别为13例,15例和12例)和健康患者(18例);由临床医生(30 ml)在装有EDTA的静脉血真空收集管中收集外周血样品,并通过Ficoll梯度离心分离外周血单核细胞。使用Trizol试剂提取RNA。使用TaqMan低密度阵列(TLDA)获得基因表达数据,该阵列包含通过算法选择的96个基因,并通过使用非参数Mann-Whitney U检验在Prism中进行了统计分析(P值,结果此处表明,使用一组96个与疾病相关的基因,并测量外周血来源的单核细胞中的mRNA表达水平;我们可以鉴定出将每种疾病与健康对照区分开的疾病特异性基因;另外还有一组五个基因,例如ADM,AQP9,CXCL2 ,IL10和NAMPT可以区分出慢性炎症患者和健康对照者的所有样本,还发现了将疾病分层的基因,并在每种情况下分别区分了不同的亚型或不同的预后状态。炎症表明这些疾病在发病机理上具有共同背景,但仍可通过周围环境加以分离l血液基因表达。重要的是,所鉴定的基因可以与包括改变的炎症反应在内的重叠生物学过程相关。基于此类标记的基因板可在个性化药物的开发,监测疾病进展中起主要作用,并可导致鉴定慢性炎症中新的潜在药物靶标。

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