系统性红斑狼疮、系统性硬皮病和皮肌炎患者 CD4+T 细胞中的异常 DNA 甲基化。

Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis.

机构信息

Department of Dermatology, Epigenetic Research Centre, Second Xiangya Hospital, Central South University, Changsha, China.

出版信息

Scand J Rheumatol. 2009;38(5):369-74. doi: 10.1080/03009740902758875.

DOI:10.1080/03009740902758875

PMID:19444718

Abstract

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.

摘要

目的

T 细胞 DNA 低甲基化被认为是导致全身性红斑狼疮（SLE）发展的原因之一。然而，目前尚不清楚其他结缔组织疾病（如系统性硬皮病[SSc]和皮肌炎[DM]）是否存在 T 细胞 DNA 甲基化受损的情况。

方法

我们定量分析了 12 名健康供体和 SLE、SSc 和 DM 患者（每组 10 名患者）CD4+T 细胞中的总体甲基化水平。采用逆转录聚合酶链反应（RT-PCR）测量 DNA 甲基转移酶（DNMTs）和甲基-CpG 结合域蛋白（MBDs）的 mRNA 水平。

结果

与对照组相比，SLE（活动期和非活动期）和 SSc 患者的 CD4+T 细胞 DNA 明显低甲基化，但 DM 患者的 DNA 无明显变化。SLE 组的 DNMT1 和 MBD4 mRNA 的平均表达水平显著降低，而 MBD2 和 MeCP2 mRNA 的水平显著升高。SSc 组的 DNMT1、MBD3 和 MBD4 mRNA 显著降低，而 DM 组的 MBD2 和 MeCP2 mRNA 显著升高。SLE 样本中与 DNMT1 相关的总体 DNA 低甲基化程度与相对水平呈正相关，SSc 样本中与 MBD4 相关的总体 DNA 低甲基化程度与相对水平呈正相关。