PDF(Pubmed)
Abstract：
Patients admitted to the intensive care unit (ICU) often experience endotoxemia, nosocomial infections and sepsis. Polymorphonuclear and monocytic myeloid-derived suppressor cells (PMN-MDSCs and M-MDSCs) can have an important impact on the development of infectious diseases, but little is known about their potential predictive value in critically ill patients. Here, we used unsupervised flow cytometry analyses to quantify MDSC-like cells in healthy subjects challenged with endotoxin and in critically ill patients admitted to intensive care units and at risk of developing infections. Cells phenotypically similar to PMN-MDSCs and M-MDSCs increased after endotoxin challenge. Similar cells were elevated in patients at ICU admission and normalized at ICU discharge. A subpopulation of M-MDSC-like cells expressing intermediate levels of CD15 (CD15int M-MDSCs) was associated with overall mortality (p = 0.02). Interestingly, the high abundance of PMN-MDSCs and CD15int M-MDSCs was a good predictor of mortality (p = 0.0046 and 0.014), with area under the ROC curve for mortality of 0.70 (95% CI = 0.4-1.0) and 0.86 (0.62-1.0), respectively. Overall, our observations support the idea that MDSCs represent biomarkers for sepsis and that flow cytometry monitoring of MDSCs may be used to risk-stratify ICU patients for targeted therapy.
摘要：
入住重症监护病房（ICU）的患者经常会出现内毒素血症，医院感染和败血症。多形核和单核细胞髓源性抑制细胞（PMN-MDSCs和M-MDSCs）可对感染性疾病的发生发展产生重要影响。但对其在危重患者中的潜在预测价值知之甚少。这里,我们使用无监督流式细胞术分析对接受内毒素攻击的健康受试者和入住重症监护病房并有感染风险的危重患者的MDSC样细胞进行定量.与PMN-MDSC和M-MDSC表型相似的细胞在内毒素攻击后增加。ICU入院时患者的相似细胞升高，ICU出院时恢复正常。表达中等水平CD15的M-MDSC样细胞亚群(CD15intM-MDSC)与总死亡率相关(p=0.02)。有趣的是,PMN-MDSCs和CD15intM-MDSCs的高丰度是死亡率的良好预测因子(p=0.0046和0.014),死亡率的ROC曲线下面积为0.70（95％CI=0.4-1.0）和0.86（0.62-1.0），分别。总的来说,我们的观察结果支持以下观点:MDSCs是脓毒症的生物标志物,流式细胞术监测MDSCs可用于ICU患者靶向治疗的风险分层.
