DNA methylation of human endogenous retrovirus in systemic lupus erythematosus
DNA methylation of human endogenous retrovirus in systemic lupus erythematosus
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DOI：
10.1038/jhg.2013.6
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发表时间：
2013-05-01
影响因子：
3.5
通讯作者：
Hirankarn, Nattiya
中科院分区：
文献类型：
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作者：
Nakkuntod, Jeerawat;Sukkapan, Pattadon;Hirankarn, Nattiya
先前的研究报道，来自活动性系统性红斑狼疮（SLE）患者的T细胞在多个基因的启动子处含有整体低甲基化和去甲基化，这可能有助于该疾病的发病机制。目前，关于 SLE 患者逆转录元件甲基化的数据很少。我们通过使用联合亚硫酸氢盐限制性分析-散布重复序列（COBRA-IRS）估计并比较了正常和 SLE CD3 + CD4 + T 淋巴细胞、CD8 + T 和 B 淋巴细胞中人内源性逆转录病毒 (HERV)-E 和 HERV-K 的甲基化水平。活动性SLE的CD3+CD4+T淋巴细胞中HERV-E LTR2C甲基化水平显着低于非活动性SLE和正常对照（P分别为0.023和0.035）。令人惊讶的是，与活动性 SLE 和正常对照相比，非活动性 SLE 患者的 CD3 + CD4 + T 淋巴细胞中显着检测到 HERV-K LTR5_Hs 低甲基化（分别为 P = 0.027 和 0.002）。与正常对照相比，还检测到 B 细胞中 HERV-K LTR5_Hs 的去甲基化（P = 0.048）。此外，CD3+CD4+T淋巴细胞中HERV-E LTR2C的低甲基化与活动性SLE中的淋巴细胞减少呈正相关，而HERV-K LTR5+Hs的低甲基化与补体活性和系统性红斑狼疮疾病活动指数评分显着相关。总之，对于 SLE 患者的每个淋巴细胞亚群，IRS 低甲基化被发现具有类型特异性。需要进一步的研究来证实和解释这些观察结果。
Previous studies have reported that T cells from active systemic lupus erythematosus (SLE) patients contained global hypomethylation and demethylation at the promoter of several genes, which may contribute to the pathogenesis of the disease. Currently there are scarce data on methylation of retroelements in patients with SLE. We estimated and compared the methylated levels of human endogenous retroviruses (HERV)-E and HERV-K in normal and SLE CD3 + CD4 + T lymphocytes, CD8 + T and B lymphocytes by using combined bisulfite restriction analysis-interspersed repetitive sequences (COBRA-IRS). HERV-E LTR2C methylation level in CD3 + CD4 + T lymphocytes of active SLE was significantly lower than inactive SLE and normal controls (P = 0.023 and 0.035, respectively). Surprisingly, HERV-K LTR5_Hs hypomethylation was significantly detected in CD3 + CD4 + T lymphocytes from patients with inactive SLE when compared with the active SLE and normal controls (P = 0.027 and 0.002, respectively). Demethylation of HERV-K LTR5_Hs in B cells was also detected when compared with the normal controls (P = 0.048). Furthermore, the hypomethylation of HERV-E LTR2C in CD3 + CD4 + T lymphocytes was positively correlated with lymphopenia in active SLE, whereas the hypomethylation of HERV-K LTR5 + Hs was significantly correlated with complement activity and Systemic Lupus Erythematosus Disease Activity Index score. In summary, for each lymphocyte subset in patients with SLE, IRS hypomethylation was found to be type specific. Further studies are needed to confirm and explain these observations.