目的应用寡聚核苷酸基因表达芯片研究系统性红斑狼疮(SLE)患者与健康志愿者外周血B淋巴细胞基因表达谱的变化。方法应用包含21522条70mer长度Oligo DNA的寡聚核苷酸芯片(22K Human Genome Arrav)分别检测6例SLE患者和6名健康志愿者外周血B淋巴细胞基因表达谱,应用聚类分析法分析差异表达的基因。结果SLE患者外周血B淋巴细胞和健康志愿者B淋巴细胞之间基因表达谱有显著差异,芯片中聚类表达显著上调的基因15个,主要包括Ⅰ型干扰素(IFN)通路中的相关分子;聚类表达显著下调的基因22个,主要包括神经内分泌相关的精氨酸甲基化转移酶家族等与雌激素代谢相关的基因。进一步对这些差异表达基因进行了初步的功能分类分析,分析结果表明这些基因主要与B淋巴细胞的JAK—STAT信号通路和激素代谢相关。结论SLE患者外周血B淋巴细胞基因表达谱存在显著差异,芯片显示氨基酸代谢、激素代谢、细胞增殖和凋亡、炎症反应等相关生物学功能的改变可能参与SLE的发病。
Objective To identify the differentially expressed genes in systemic lupus erythematosus (SLE) by comparing the gene expression profile of peripheral blood B cells between SLE patients and healthy controls. Methods The total RNAs were extracted from B cells of SLE patients and normal subjects, the cDNA retro-transcribed from equal quantity mRNA were labeled with Cy3 and Cy5 fluorescence as probes. Analysis of the differentially expressed genes was carried out by hierarchical cluster method. Results Clustering analysis showed that 15 genes were up-regulated, mainly including the type Ⅰ IFN related genes. Twenty-two genes were down-regulated, mainly including estradiol metabolism related genes. While these genes were classified initially according to their functions, it was found that they played important role mainly in JAK-STAT pathway. Conclusion Significant differences are found in the expression of some functional genes in the B cells between SLE patients and healthy controls. Most of these genes are involved in amino acid metabolism, hormone metabolism, cell proliferation and apoptosis.