Focused microarray analysis of peripheral mononuclear blood cells from Churg-Strauss syndrome patients
Focused microarray analysis of peripheral mononuclear blood cells from Churg-Strauss syndrome patients
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DOI：
10.1093/dnares/dsm035
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发表时间：
2008-04-01
期刊：
影响因子：
4.1
通讯作者：
Nojima, Hiroshi
中科院分区：
文献类型：
--
作者：
Tougan, Takahiro;Onda, Hiroaki;Nojima, Hiroshi
DNA诊断是有用的，但受到困难的伦理问题的阻碍。此外，它不能提供足够的信息，环境因素是重要的某些疾病的发病机制。然而，这对于RNA诊断不是问题，RNA诊断评估所讨论的基因的表达。我们在这里报告了一种新的RNA诊断工具，可以与外周血单核细胞（PBMC）。为了建立这种工具，我们鉴定了290个在正常PBMC中高度表达但在正常人成纤维细胞TIG-1中不表达的基因。这些基因主要在PBMC中表达，被命名为PREP，包括50个未表征的基因。然后，我们对7例Churg-Strauss综合征（CSS）（一种小血管坏死性血管炎）患者的PBMC进行了PREP基因聚焦微阵列分析。我们发现，PREP 135（类辅乳糖酶蛋白），PREP 77（saposin），PREP 191（组织蛋白酶D），PREP 234（c-fgr），和PREP 136（溶菌酶）在所有7例CSS患者中高度上调。另外28个基因也被上调，尽管幅度更小，3个基因在所有CSS患者中被下调。这些上调和下调的基因的性质表明，患者的免疫系统在应对入侵的微生物时被激活。这些观察结果表明，PBMCs的聚焦微阵列分析可能是一种实用，有用和低成本的床边诊断工具。
DNA diagnostics are useful but are hampered by difficult ethical issues. Moreover, it cannot provide enough information on the environmental factors that are important for pathogenesis of certain diseases. However, this is not a problem for RNA diagnostics, which evaluate the expression of the gene in question. We here report a novel RNA diagnostics tool that can be employed with peripheral blood mononuclear cells (PBMCs). To establish this tool, we identified 290 genes that are highly expressed in normal PBMCs but not in TIG-1, a normal human fibroblast cell. These genes were entitled PREP after predominantly expressed in PBMC and included 50 uncharacterized genes. We then conducted PREP gene-focused microarray analysis on PBMCs from seven cases of Churg-Strauss syndrome (CSS), which is a small-vessel necrotizing vasculitis. We found that PREP135 (coactosin-like protein), PREP77 (prosaposin), PREP191 (cathepsin D), PREP234 (c-fgr), and PREP136 (lysozyme) were very highly up-regulated in all seven CSS patients. Another 28 genes were also up-regulated, albeit more moderately, and three were down-regulated in all CSS patients. The nature of these up- and down-regulated genes suggest that the immune systems of the patients are activated in response to invading microorganisms. These observations indicate that focused microarray analysis of PBMCs may be a practical, useful, and low-cost bedside diagnostics tool.