Differential expression of genes associated with T lymphocytes function in septic patients with hypoxemia challenge.

Abstract

This study aimed to assess gene expression alterations related to T lymphocytes function and explore their potential association with hypoxemia among septic patients. This is a retrospective cohort clinical study with laboratory investigations. We studied patients enrolled in sepsis biological specimen bank from Department of Critical Care Medicine, Zhongda Hospital, fulfilling consensus criteria for sepsis without any documented immune comorbidity admitted in ICU within 48 h after onset with whole blood samples drawn within 24 h of admission. Whole genome expression by microarray assay (Human LncRNA Microarray V4.0) was compared in hypoxemia cohort versus without. Differentially expressed (DE) genes with >1 log2[fold change (FC)] and false discovery rate (FDR) <0.20 that enriched in T cell related biological process entered the adjusted analysis to identify the candidate genes. The correlation analysis within candidate genes or with clinical parameters were performed. We assessed candidate expression ex vivo in co-culture system with RAW246.7 cells and validated genes identified in prior studies of sepsis-ARDS/hypoxemia within our present study. Septic patients (n=9) with hypoxemic phenotype held higher illness severity, serum lactate and creatine, and incidence of lymphopenia compared with non-hypoxemic group (n=6). Several gene signatures related to apoptosis, inhibitory receptors, T cell immunoreceptor, transcriptions factors, toll-like receptors and cytokine and effector molecules were upregulated in hypoxemic group. Candidate genes were identified after adjustment for age, sex and presence of lymphopenia with significantly negative correlations with partial pressure of O2 in an arterial blood (PaO2) and fraction of inspiration O2 (FiO2) ratio, among which NLRP3, SOS1, ELF1 and STAT3 held an increasing expression in ex vivo validation while the others, PSMA5, CLEC4D, CD300A, PRKD2 and PSMA2 showed the opposite alteration from those in vivo. Higher illness severity and incidence of lymphopenia was observed following hypoxemia in sepsis and T cell-related gene signatures were associated with hypoxemia during sepsis.