Lymphocyte expression of EZH2 is associated with mortality and secondary infectious complications in sepsis

•EZH2 in CD4+ and CD8+ T cells was higher in septic patients than in controls.•MFI of EZH2 in CD8+ T cells on day 1 predicted death in septic patients.•Combination of EZH2 level with APACHEII enhanced the prognostic predictive ability.•Expression of EZH2 on day 3 was associated with nosocomial infection in sepsis.•Expression of EZH2 was correlated to CD14+ cells-expressing HLA-DR in sepsis. 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.