Molecular profile of peripheral blood mononuclear cells from patients with rheumatoid arthritis
Molecular profile of peripheral blood mononuclear cells from patients with rheumatoid arthritis
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DOI：
10.2119/2006-000056.edwards
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发表时间：
2007-01-01
影响因子：
5.7
通讯作者：
Pittman, Debra D.
中科院分区：
文献类型：
--
作者：
Edwards, Christopher J.;Feldman, Jeffrey L.;Pittman, Debra D.
类风湿关节炎(RA)是一种慢性炎症性关节炎。目前，类风湿关节炎的诊断可能需要几周时间，用于预测预后不良的因素并不总是可靠的。类风湿关节炎的基因表达可能由一个独特的信号组成。基因表达分析已被应用于滑膜组织以确定分子上不同类型的类风湿关节炎：然而，从滑膜关节提取的组织的表达分析是侵入性的，在临床上不实用，最近的研究表明，从癌症、多发性硬化症和狼疮患者的外周血单个核细胞(PBMC)中可以识别出独特的基因表达变化。为了确定类风湿性关节炎相关基因，我们进行了全球基因表达分析。用寡核苷酸芯片分析了9例RA患者和13例正常志愿者外周血单个核细胞的RNA。与正常外周血单核细胞相比，RA患者外周血中存在330个转录本的差异表达。差异调控基因属于不同的功能类别，包括钙结合、伴侣、细胞因子、转录、翻译、信号转导、细胞外基质、细胞膜、线粒体、核糖体、结构、酶和蛋白水解酶等基因。K近邻分析确定了29个在RA中优先表达的转录本。在RA易感基因6p21.3上，有10个基因在RA患者外周血单核细胞中表达增强。这些结果提示，在分子水平上分析类风湿性关节炎患者的外周血单核细胞可以提供一组候选基因，这些候选基因可以产生一个容易获得的基因标记，以帮助早期诊断和治疗。
Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. Currently, diagnosis of RA may take several weeks, and factors used to predict a poor prognosis are not always reliable. Gene expression in RA may consist of a unique signature. Gene expression analysis has been applied to synovial tissue to define molecularly distinct forms of RA: however, expression analysis of tissue taken from a synovial joint is invasive and clinically impractical, Recent studies have demonstrated that unique gene expression changes can be identified in peripheral blood mononuclear cells (PBMCs) from patients with cancer, multiple sclerosis, and lupus. To identify RA disease-related genes, we performed a global gene expression analysis. RNA from PBMCs of 9 RA patients and 13 normal volunteers was analyzed on an oligonucleotide array. Compared with normal PBMCs, 330 transcripts were differentially expressed in RA. The differentially regulated genes belong to diverse functional classes and include genes involved in calcium binding, chaperones, cytokines, transcription, translation, signal transduction, extracellular matrix, integral to plasma membrane, integral to intracellular membrane, mitochondrial, ribosomal, structural, enzymes, and proteases. A k-nearest neighbor analysis identified 29 transcripts that were preferentially expressed in RA. Ten genes with increased expression in RA PBMCs compared with controls mapped to a RA susceptibility locus, 6p21.3. These results suggest that analysis of RA PBMCs at the molecular level may provide a set of candidate genes that could yield an easily accessible gene signature to aid in early diagnosis and treatment.