白塞病外周血白细胞差异表达基因谱的发现和验证

目的 建立白塞病(BD)外周血白细胞差异表达基因谱,探讨BD致病基因.方法 应用Affymetrix寡核苷酸基因芯片研究3对未经治BD和健康人外周血白细胞,建立差异表达基因谱;从中选取B细胞淋巴瘤6(BCL6)、白细胞来源的精氨酸氨基肽酶(LRAP)、可诱导的T细胞共刺激分子配体(ICOSLG)和膜表面金属蛋白内切酶(MME)4个基因,设立BD组、健康组、系统性红斑狼疮(SLE)组和类风湿关节炎(RA)组,采用实时定量一聚合酶链反应验证其表达水平.结果 ①在国际上首次建立了BD外周血白细胞差异表达基因谱,包含差异表达基因146个,其中上调基因89个,下调基因57个.②上述4个基因表达水平在BD活动期均显著高于健康对照组,在缓解期下降;其中BCL6、MME表达水平也显著高于SLE组和RA组.结论 ①本研究为在基因水平上进一步揭示BD的发病机制提供了线索;②首次证实了上述4个基因的表达水平与BD的活动性有关;分析表明肿瘤坏死因子(TNF)-α和干扰素(IFN)-γ调控BCL6、ICOSLG和LRAP表达水平,可能是一个新发现的致病环节;MME基因可能成为利于BD诊断的检测标记.

Building-up and verification of the differential gene expression profile of peripheral blood leukocytes in Beh(c)et's disease

Objective To explore the pathogenic genes relevant to Behcet's disease (BD) by building the differentail gene expression profiles of peripheral blood leukocytes in BD. Methods Oligonucleotide gene array from Affymetrix Company was applied to study the differed expression levels of whole genome between three age and sex matched BD patients and normal controls. Four genes, BCL6, LRAP, ICOSLG and MME, were selected to be tested for gene expression levels by real-time PCR in the groups of BD, normol controls (NC), Lupus and rheumatoid arthritis (RA) peticnts. Results ① Differential gene expression profile of BD compared to that of normal controls was built up. It contained 89 up-regulated and 57 down-regulated genes. ② Four genes mentioned above had significantly higher expression levels in active BD patients than those in NC but had lower exoression levels in stable BD patients. The expression levels of BCL6 and MME were also proved to be increased significantly in BD than in RA and SLE patients. Conclusion ① Our work shed some light on further research of the etiopathogenesis of BD. ② The expression levels of the four genes are proved to be relevant to BD the first time by us. Further analysis showes that TNF-α and IFN-γ can up-regulate the expression levels of BCL6, LRAP and ICOSLG which may be novel to BD. The MME gene is expressed on the surface of cells, which is convenient for test and may potentially be a marker for the diagnosis of BD.