Han G-M, Chen S-L, Shen N, Ye S, Bao C-D, Gu Y-Y
Department of Rheumatology, Nanjing First Hospital, Nanjing Medical University, China.
Genes Immun. 2003 Apr;4(3):177-86. doi: 10.1038/sj.gene.6363966.
Epidemiologic studies suggest a strong genetic component for susceptibility to systemic lupus erythematosus (SLE). To investigate the genetic mechanism of pathogenesis of SLE, we studied the difference in gene expression of peripheral blood cells between 10 SLE patients and 18 healthy controls using oligonucleotide microarray. When gene expression for patients was compared to the mean of normal controls, among the 3002 target genes, 61 genes were identified with greater than a two-fold change difference in expression level. Of these genes, 24 were upregulated and 37 downregulated in at least half of the patients. By the Welch's ANOVA/Welch's t-test, all these 61 genes were significantly different (P<0.05) between SLE patients and normal controls. Among these genes with differential expression, IFN-omega and Ly6E (TSA-1/Sca-2) may play an important role in the mechanism of SLE pathogenesis. TSA-1 antigens may represent an important alternative pathway for T-cell activation that may be involved in IFN-mediated immunomodulation. Hierarchical clustering showed that patient samples were clearly separated from controls based on their gene expression profile. These results demonstrate that high-density oligonucleotide microarray has the potential to explore the mechanism of pathogenesis of systemic lupus erythematosus.
流行病学研究表明，系统性红斑狼疮（SLE）易感性存在很强的遗传因素。为了研究SLE发病的遗传机制，我们使用寡核苷酸微阵列研究了10例SLE患者和18例健康对照外周血细胞基因表达的差异。将患者的基因表达与正常对照的均值进行比较时，在3002个靶基因中，有61个基因的表达水平差异超过两倍。在这些基因中，至少一半患者中有24个基因上调，37个基因下调。通过韦尔奇方差分析/韦尔奇t检验，这61个基因在SLE患者和正常对照之间均有显著差异（P<0.05）。在这些差异表达的基因中，IFN-ω和Ly6E（TSA-1/Sca-2）可能在SLE发病机制中起重要作用。TSA-1抗原可能代表T细胞激活的一条重要替代途径，可能参与IFN介导的免疫调节。层次聚类显示，患者样本根据其基因表达谱与对照明显分开。这些结果表明，高密度寡核苷酸微阵列有潜力探索系统性红斑狼疮的发病机制。
