狼疮患者CD4+ T细胞中异常的组蛋白修饰模式。

Abnormal histone modification patterns in lupus CD4+ T cells.

作者信息

Hu Nan, Qiu Xiangning, Luo Yongqi, Yuan Jun, Li Yaping, Lei Wenzhi, Zhang Guiying, Zhou Ying, Su Yuwen, Lu Qianjin

机构信息

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

出版信息

J Rheumatol. 2008 May;35(5):804-10. Epub 2008 Apr 1.

PMID:18398941

Abstract

OBJECTIVE

To investigate alterations in histone modifications in patients with systemic lupus erythematosus (SLE).

METHODS

Global histone H3/H4 acetylation and H3K4/H3K9 methylation in CD4+ T cells from 20 SLE patients and 10 healthy control subjects were assayed using the EpiQuik global histone H3/H4 acetylation and H3K4/H3K9 methylation assay kits. mRNA levels of 12 members of 3 classes of chromatin modifier genes were measured by real-time quantitative polymerase chain reaction.

RESULTS

Global histone H3 and H4 hypoacetylation was observed in active lupus CD4+ T cells compared with controls (p = 0.002 and p = 0.009, respectively). The degree of histone H3 acetylation correlated negatively with increased disease activity in lupus patients as measured by SLEDAI (r = -0.889, p = 0.044). We found global histone H3K9 hypomethylation in both active and inactive lupus CD4+ T cells, compared with controls (p = 0.001, p = 0.003, respectively). However, global levels of H3K4 methylation were not different between patients and controls. SIRT1 mRNA levels were significantly increased in active lupus CD4+ T cells compared with controls (p < 0.001), while mRNA levels of CREBBP, P300, HDAC2, HDAC7, SUV39H2, and EZH2 were significantly downregulated in patients with active lupus (p < 0.001, p < 0.001, p = 0.01, p < 0.001, p = 0.003, p = 0.001, respectively).

CONCLUSION

Histone modifications appear abnormal in CD4+ T cells in SLE.

摘要

目的

研究系统性红斑狼疮（SLE）患者组蛋白修饰的变化。

方法

使用EpiQuik全球组蛋白H3/H4乙酰化和H3K4/H3K9甲基化检测试剂盒，检测20例SLE患者和10名健康对照者CD4+ T细胞中的整体组蛋白H3/H4乙酰化和H3K4/H3K9甲基化情况。通过实时定量聚合酶链反应测量3类染色质修饰基因中12个成员的mRNA水平。

结果

与对照组相比，活动期狼疮患者的CD4+ T细胞中观察到整体组蛋白H3和H4低乙酰化（分别为p = 0.002和p = 0.009）。狼疮患者中，通过SLEDAI测量，组蛋白H3乙酰化程度与疾病活动度增加呈负相关（r = -0.889，p = 0.044）。与对照组相比，我们发现活动期和非活动期狼疮患者的CD4+ T细胞中均存在整体组蛋白H3K9低甲基化（分别为p = 0.001，p = 0.003）。然而，患者和对照组之间H3K4甲基化的整体水平没有差异。与对照组相比，活动期狼疮患者的CD4+ T细胞中SIRT1 mRNA水平显著升高（p < 0.001），而活动期狼疮患者中CREBBP、P300、HDAC2、HDAC7、SUV39H2和EZH2 的mRNA水平显著下调（分别为p < 0.001，p < 0.001，p = 0.01，p < 0.001，p = 0.003，p = 0.001）。