Neutrophil-derived circulating free DNA (cf-DNA/NETs):: A potential prognostic marker for posttraumatic development of inflammatory second hit and sepsis
Neutrophil-derived circulating free DNA (cf-DNA/NETs):: A potential prognostic marker for posttraumatic development of inflammatory second hit and sepsis
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DOI：
10.1097/shk.0b013e31816a6bb1
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发表时间：
2008-10-01
期刊：
影响因子：
3.1
通讯作者：
Windolf, Joachim
中科院分区：
文献类型：
--
作者：
Margraf, Stefan;Loegters, Tim;Windolf, Joachim
“中性粒细胞胞外陷阱”（NETs）的释放已被鉴定为先天免疫中的一种新型免疫应答。嗜中性粒细胞胞外陷阱由嗜中性粒细胞衍生的循环游离DNA（cf-DNA）、组蛋白和嗜中性粒细胞胞质衍生的蛋白质如蛋白酶组成。在这里，我们研究了血浆cf-DNA/NETs对多发性创伤后脓毒症发展和死亡率的预测价值。在对45名多发性创伤（损伤严重度评分>16）患者的前瞻性初步研究中，直接定量血浆中的cf-DNA。从入院到我们的创伤中心直到第10天，每天连续采集血样。由于重症监护室（ICU）停留时间少于3天，因此排除了8例患者，因此对37例患者进行了评价。将cf-DNA/NETs的时间动力学与C反应蛋白（CRP）、白细胞介素（IL）6、白细胞计数和髓过氧化物酶进行比较。根据ICU的损伤严重程度评分、多器官功能障碍评分、序贯器官衰竭评估和简化急性生理学评分11计算损伤严重程度。最初的高cf-DNA/NET值（>800 ng/mL）与第5至9天之间复发性增加的值与随后的脓毒症、多器官衰竭和死亡相关。与cf-DNA/NETs一起，IL-6在入院后显著升高。然而，IL-6未指示第二次命中的发展。与cf-DNA/NET相反，在有和没有发生脓毒症的患者之间没有观察到CRP动力学的差异。循环游离DNA/NET动力学与多器官功能障碍评分、脓毒症相关器官衰竭评估、白细胞计数和部分髓过氧化物酶动力学密切相关。循环游离DNA/NETs似乎是计算损伤严重程度和/或预测ICU炎症二次打击的有价值的额外标志物。然而，对严重受伤患者的大型临床试验应该证实嗜中性粒细胞衍生的cf-DNA/NET的预后价值。
The release of "neutrophil extracellular traps" (NETs) has been identified as a novel immune response in innate immunity. Neutrophil extracellular traps are composed of neutrophil-derived circulating free DNA (cf-DNA), histones, and neutrophil cytoplasm-derived proteins such as proteases. Here, we studied the putative predictive value of plasma cf-DNA/NETs for the development of sepsis and mortality after multiple trauma. In a prospective pilot study with 45 multiple trauma (Injury Severity Score >16) patients, cf-DNA was directly quantified in plasma. Blood samples were sequentially obtained daily from admission to our Trauma Center until day 10. Because of limited intensive care unit (ICU) stay of less than 3 days, 8 patients have been excluded, resulting in 37 patients that were evaluated. Time kinetics of cf-DNA/NETs was compared with C-reactive protein (CRP), interleukin (IL) 6, leukocyte counts, and myeloperoxidase. The severity of the injury was calculated on the basis of the Injury Severity Score, as well as Multiple Organ Dysfunction Score, Sequential Organ Failure Assessment, and Simplified Acute Physiology Score 11 on ICU. Initially high cf-DNA/NETs values (>800 ng/mL) with recurrent increased values between days 5 to 9 were associated with subsequent sepsis, multiple organ failure, and death. In conjunction with cf-DNA/NETs, IL-6 was significantly elevated after admission. However, the development of a second hit was not indicated by IL-6. In contrast to cf-DNA/NETs, no difference in CRP kinetics was observed between patients with and without development of sepsis. Circulating free DNA/NETs kinetics rather followed kinetics of Multiple Organ Dysfunction Score, Sepsis-related Organ Failure Assessment, leukocyte counts, and partially of myeloperoxidase. Circulating free DNA/NETs seems to be a valuable additional marker for the calculation of injury severity and/or prediction of inflammatory second hit on ICU. However, a large clinical trial with severely injured patients should confirm the prognostic value of neutrophil-derived cf-DNA/NETs.