Recent studies have shown that epigenetic factors may affect immune responses. We previously reported that histone methyltransferase enhancer of zeste homolog 2 (EZH2) was involved in the innate inflammatory responses both in animal model of sepsis and in septic patients. In this study, we prospectively evaluated EZH2 expression kinetics in peripheral CD4+ and CD8+ T cells and HLA-DR expression in CD14+ cells from 48 patients with sepsis and 48 healthy controls. Results showed higher level of EZH2 in CD4+ T cells and CD8+ T cells in sepsis patients than in controls. Meanwhile, EZH2 expression was correlated with CD27 status on T cells. Mean fluorescence intensity (MFI) of EZH2 in CD8+ T cells on day 1 independently predicted death in septic patients. Also, the combination of CD8+ T cell EZH2 expression with APACHEII and SOFA score could enhance the prognostic predictive ability. Moreover, multivariate logistic regression analysis showed that increased expression (proportion and MFI) of EZH2 in CD4+ and CD8+ lymphocytes on day 3 were independently associated with nosocomial infection in septic patients. Additionally, spearman correlation analysis indicated that the levels of EZH2 in CD4+ T cells and CD8+ T cells correlated to CD14+ cells-expressing HLA-DR in patients with sepsis at each time point. Overall, these findings suggest that EZH2 in CD4+ T cells or/and CD8+ T cells may be a novel biomarker for predicting adverse outcomes (mortality and secondary infectious complications) in patients with sepsis.

最近的研究表明，表观遗传因素可能会影响免疫反应。我们以前曾报道过，zeste同源物2（EZH2）的组蛋白甲基转移酶增强子参与了败血症动物模型和败血症患者的先天性炎症反应。在这项研究中，我们前瞻性评估了48位脓毒症患者和48位健康对照者的外周CD4 +和CD8 + T细胞中EZH2表达动力学以及CD14 +细胞中HLA-DR表达。结果显示败血症患者的CD4 + T细胞和CD8 + T细胞中EZH2水平高于对照组。同时，EZH2表达与T细胞上CD27状态相关。第1天，CD8 + T细胞中EZH2的平均荧光强度（MFI）独立预测败血症患者的死亡。也，CD8 + T细胞EZH2表达与APACHEII和SOFA评分相结合可提高预后预测能力。此外，多因素logistic回归分析显示，败血病患者第3天CD4 +和CD8 +淋巴细胞中EZH2表达的增加（比例和MFI）与医院感染无关。此外，spearman相关分析表明，在每个时间点，脓毒症患者CD4 + T细胞和CD8 + T细胞中EZH2的水平与表达CD14 +细胞的HLA-DR相关。总体而言，这些发现表明CD4 + T细胞或CD8 + T细胞中的EZH2可能是预测败血症患者不良结局（死亡率和继发感染并发症）的新生物标记。多元logistic回归分析显示，败血病患者第3天CD4 +和CD8 +淋巴细胞中EZH2表达的增加（比例和MFI）与医院感染无关。此外，spearman相关分析表明，在每个时间点，脓毒症患者CD4 + T细胞和CD8 + T细胞中EZH2的水平与表达CD14 +细胞的HLA-DR相关。总体而言，这些发现表明CD4 + T细胞或CD8 + T细胞中的EZH2可能是预测败血症患者不良结局（死亡率和继发感染并发症）的新生物标记。多元logistic回归分析显示，败血病患者第3天CD4 +和CD8 +淋巴细胞中EZH2表达的增加（比例和MFI）与医院感染无关。此外，spearman相关分析表明，在每个时间点，脓毒症患者CD4 + T细胞和CD8 + T细胞中EZH2的水平与表达CD14 +细胞的HLA-DR相关。总体而言，这些发现表明CD4 + T细胞或CD8 + T细胞中的EZH2可能是预测败血症患者不良结局（死亡率和继发感染并发症）的新生物标记。Spearman相关分析表明，脓毒症患者在每个时间点CD4 + T细胞和CD8 + T细胞中EZH2的水平与表达CD14 +细胞的HLA-DR相关。总体而言，这些发现表明CD4 + T细胞或CD8 + T细胞中的EZH2可能是预测败血症患者不良结局（死亡率和继发感染并发症）的新生物标记。Spearman相关分析表明，脓毒症患者在每个时间点CD4 + T细胞和CD8 + T细胞中EZH2的水平与表达CD14 +细胞的HLA-DR相关。总体而言，这些发现表明CD4 + T细胞或CD8 + T细胞中的EZH2可能是预测败血症患者不良结局（死亡率和继发感染并发症）的新生物标记。