Peripheral blood gene expression profiling in rheumatoid arthritis
Peripheral blood gene expression profiling in rheumatoid arthritis
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DOI：
10.1038/sj.gene.6364209
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发表时间：
2005-08-01
影响因子：
5
通讯作者：
Gregersen, PK
中科院分区：
文献类型：
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作者：
Batliwalla, FM;Baechler, EC;Gregersen, PK
我们使用Affymetrix U95Av2阵列对29例活动性类风湿关节炎（RA）患者和21例对照者的外周血单个核细胞（PBMCs）进行了基因表达谱分析。通过聚类分析，我们发现与对照组相比，RA患者PBMCs中81个基因的表达模式发生了显著变化（P < 0.001）。这些基因中的许多都与两个研究群体中单核细胞计数的差异相关，我们发现这些基因的很大一部分在单核细胞中特异性高水平表达。此外，还进行了逻辑回归分析，以确定在类风湿关节炎和对照样本分类中表现最好的基因。谷氨酰环化酶、IL1RA、S100A12（也称为calgranulin或EN-RAGE）和grb2相关结合蛋白（GAB2）是最重要的鉴别因子。与以往的数据一起，S100A12在RA患者中的过表达强调了RAGE通路在疾病发病机制中的可能重要性。GAB2是一种参与调节磷酸酶功能的细胞内衔接分子，由于最近发现细胞内磷酸酶PTPN22是RA的危险基因，因此GAB2的表达改变引起了人们的特别关注。这些数据表明，对外周血中基因表达模式的详细研究可以为了解疾病的发病机制提供帮助。然而，同样清楚的是，为了评估完全基因表达谱作为识别疾病亚群的手段，或定义RA治疗结果和反应的生物标志物，需要更大的样本量。
We carried out gene expression profiling of peripheral blood mononuclear cells ( PBMCs) in 29 patients with active rheumatoid arthritis ( RA) and 21 control subjects using Affymetrix U95Av2 arrays. Using cluster analysis, we observed a significant alteration in the expression pattern of 81 genes ( P < 0.001) in the PBMCs of RA patients compared with controls. Many of these genes correlated with differences in monocyte counts between the two study populations, and we show that a large fraction of these genes are specifically expressed at high levels in monocytes. In addition, a logistic regression analysis was performed to identify genes that performed best in the categorization of RA and control samples. Glutaminyl cyclase, IL1RA, S100A12 ( also known as calgranulin or EN-RAGE) and Grb2-associated binding protein ( GAB2) were among the top discriminators. Along with previous data, the overexpression of S100A12 in RA patients emphasizes the likely importance of RAGE pathways in disease pathogenesis. The altered expression of GAB2, an intracellular adaptor molecule involved in regulating phosphatase function, is of particular interest given the recent identification of the intracellular phosphatase PTPN22 as a risk gene for RA. These data suggest that a detailed study of gene expression patterns in peripheral blood can provide insight into disease pathogenesis. However, it is also clear that substantially larger sample sizes will be required in order to evaluate fully gene expression profiling as a means of identifying disease subsets, or defining biomarkers of outcome and response to therapy in RA.