Objective: To analyze peripheral blood interleukin-6 (IL-6) promoter DNA methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE). Methods: Blood samples of 41 adult patients with SLE and 20 healthy controls were collected.The methylation status of IL-6 promoter was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR.Correlations between IL-6 promoter methylation status and clinical features or laboratory findings in patients with SLE were analyzed. Results: The levels of IL-6 mRNA were significantly higher in peripheral blood of SLE.DNA methylation levels of IL-6 promoter were reduced in SLE patients as compared with healthy controls.The methylation status and expression of IL-6 in peripheral blood reflected the levels in peripheral blood mononuclear cells (PBMCs). Significantly positive correlation was found between IL-6 hypomethylation and renal disorder, as well as hypocomplementemia in patients with SLE. Conclusion: Hypomethylation of interleukin-6 promoter in peripheral blood might be involved in the etiology of SLE.
目的： 分析系统性红斑狼疮(SLE)患者外周血中白细胞介素(IL)-6启动子DNA甲基化状态及其在系统性红斑狼疮发病机制中的作用。 方法： 选择41例在广州市第一人民医院风湿免疫内科住院的活动期SLE患者和20例健康对照者为研究对象，用甲基化特异性PCR(MSP)方法检查全血及外周血单个核细胞(PBMC)中IL-6启动子DNA甲基化状态，用qRT-PCR方法检测IL-6mRNA的表达水平，分析IL-6启动子DNA甲基化状态与SLE患者实验室参数和脏器损害的关系。 结果： (1)IL-6mRNA在SLE患者外周血及PBMC中的表达均增加，SLE患者外周血中IL-6的表达是对照组外周血IL-6表达的(1.63±0.69)倍，SLE患者PBMC中IL-6的表达是对照组PBMC中IL-6表达的(1.66±0.71)倍，差异均有统计学意义(均P<0.001)；(2)32例(78%)SLE患者外周血中IL-6基因发生低甲基化，较正常对照样本中6例(30%)DNA低甲基化发生率高(P<0.05)，外周血中IL-6基因甲基化状态与该患者PBMC中甲基化状态的差异无统计学意义；(3)SLE患者外周血IL-6基因DNA甲基化状态与补体C3、C4的降低相关(P<0.05)；(4)SLE患者外周血IL-6基因DNA低甲基化状态与肾脏损害相关(P<0.05)。 结论： SLE患者外周血中IL-6启动子DNA呈低甲基化状态，且与补体C3、C4的降低及肾脏损害相关，提示IL-6启动子DNA低甲基化可能参与SLE的发病。.
Keywords: DNA methylation; Interleukin-6; Peripheral blood; Systemic lupus erythematosus.