Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis
Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis
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DOI：
10.1080/03009740902758875
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发表时间：
2009-01-01
影响因子：
2.1
通讯作者：
Lu, Q.
中科院分区：
文献类型：
--
作者：
Lei, W.;Luo, Y.;Lu, Q.
目的：T细胞DNA低甲基化被认为与系统性红斑狼疮(SLE)的发生有关。然而，目前尚不清楚其他结缔组织疾病是否存在T细胞DNA甲基化受损，如系统性硬化症(SSC)和皮肌炎(DM)。方法：我们量化了12名健康献血者和SLE、SSC和DM患者(每组10例)CD4+T细胞的整体甲基化。用逆转录聚合酶链式反应(RT-PCR)检测DNA甲基转移酶(DNMTs)和甲基CpG结合域蛋白(MBDS)的mRNA水平。结果：SLE患者(活动期和非活动期)和SSC患者的CD4+T细胞DNA甲基化水平明显低于正常对照组，而DM患者无明显变化。SLE组DNMT1和MBD4的平均表达水平显著低于对照组，而Mbd2和MeCP2的平均表达水平显著高于对照组。SSc组DNMT1、MBD3和MBD4基因表达显著降低，而DM组Mbd2和MeCP2基因表达显著升高。整体DNA低甲基化程度与SLE样本中DNMT1和SSC样本中MBD4的相对水平呈正相关。结论：DNA甲基化水平降低和CD4+T细胞中甲基化相关基因的异常表达与SLE和SSC有关。
Objectives: T-cell DNA hypomethylation is thought to contribute to the development of systemic erythematosus lupus (SLE). However, it is unknown whether impaired T-cell DNA methylation occurs in other connective tissue diseases, such as systemic sclerosis (SSc) and dermatomyositis (DM).Methods: We quantified global methylation in CD4+ T cells from 12 healthy donors and patients with SLE, SSc, and DM (10 patients in each group). mRNA levels of DNA methyltransferases (DNMTs) and methyl-CpG-binding domain proteins (MBDs) were measured by reverse transcription polymerase chain reaction (RT-PCR).Results: CD4+ T-cell DNA from patients with SLE (both active and inactive) and SSc, but not DM, was significantly hypomethylated relative to controls. The average expression levels of DNMT1 and MBD4 mRNA were significantly lower whereas MBD2 and MeCP2 mRNA levels were significantly higher in the SLE group. DNMT1, MBD3, and MBD4 mRNA was significantly decreased in the SSc group, whereas MBD2 and MeCP2 mRNA was significantly higher in the DM group. The degree of global DNA hypomethylation correlated positively with the relative level of DNMT1 across SLE samples and MBD4 across the SSc samples.Conclusion: Reduced DNA methylation and abnormal expression of methylation-related genes in CD4+ T cells are associated with SLE and SSc.