State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
Mol Immunol. 2011 Jul;48(12-13):1525-31. doi: 10.1016/j.molimm.2011.04.012. Epub 2011 May 6.
CD70 (TNFSF7), as a methylation susceptive immune gene, was hypomethylated in some autoimmune diseases. To investigate the status of CD70 methylation and the expressions of genes that regulated methylation in immune thrombocytopenia (ITP) patients, the expressions of CD70 mRNA and protein in CD4(+) T cells from ITP and controls were measured respectively by real-time PCR and flow cytometry. Methylation specific high resolution melting (MS-HRM) technology was applied to detect CD70 promoter methylation indices. Transcription levels of DNA methyltransferases (DNMTs), methylated CpG binding protein 2 (MBD2) were measured. The results showed that CD70, DNMTs and MBD2 was over expressed and methylation indices of CD70 promoter in CD4(+) T cells from ITP patients were lower than that from healthy controls. The transcription levels of CD70 showed significantly inverse correlation with methylation indices in ITP patients but significantly positive correlation with that of DNMTs. We concluded that DNMTs functioned as demethylases as MBD2, while increased DNMTs and MBD2 may cause demethylation and over expression of CD70 in CD4(+) T cells, potentially contributing to the pathogenesis of ITP.
CD70（TNFSF7）作为一个易甲基化的免疫基因，在一些自身免疫性疾病中出现低甲基化。为了研究免疫性血小板减少症（ITP）患者中 CD70 甲基化的状态和调控甲基化的基因表达，通过实时 PCR 和流式细胞术分别测量了 ITP 患者和对照组 CD4+T 细胞中 CD70 mRNA 和蛋白的表达。应用甲基化特异性高分辨率熔解（MS-HRM）技术检测 CD70 启动子甲基化指数。测量了 DNA 甲基转移酶（DNMTs）、甲基化 CpG 结合蛋白 2（MBD2）的转录水平。结果表明，CD70、DNMTs 和 MBD2 表达上调，ITP 患者 CD4+T 细胞中 CD70 启动子的甲基化指数低于健康对照组。ITP 患者中 CD70 的转录水平与甲基化指数呈显著负相关，与 DNMTs 的转录水平呈显著正相关。我们得出结论，DNMTs 作为去甲基酶与 MBD2 一起发挥作用，而增加的 DNMTs 和 MBD2 可能导致 CD4+T 细胞中 CD70 的去甲基化和过表达，这可能有助于 ITP 的发病机制。
