Thermo Fisher Scientific, BRAHMS Biomarkers, Research Department, Hennigsdorf, Germany.
Shock. 2011 May;35(5):460-5. doi: 10.1097/SHK.0b013e3182115f40.
Oxidative stress, a situation with increased reactive oxygen species production and/or decreased antioxidant defense mechanisms, is evident in the pathogenesis of sepsis. Peroxiredoxin 4 (Prx4) is a hydrogen peroxide degrading peroxidase recently found circulating in blood of septic patients and potentially reflecting an antioxidant system in imbalance. We studied Prx4 serum levels of 79 consecutively enrolled medical intensive care unit patients. The diagnostic and prognostic performance of Prx4 was compared with other biomarkers, the APACHE II score and the SOFA score. Median Prx4 serum levels gradually increased with disease severity in patients classified on admission as having systemic immune response syndrome (2.32 arbitrary [arb.] U/L), sepsis (5.02 arb. U/L), severe sepsis (11.7 arb. U/L), or septic shock (11.4 arb. U/L). A positive correlation was found with the severity score Acute Physiological and Chronic Health Evaluation II (r = 0.27, P < 0.05) and the organ failure score Sequential Organ Failure Assessment (r = 0.55, P < 0.0001). Peroxiredoxin 4 correlated with the sepsis marker procalcitonin (r = 0.61, P < 0.0001), the inflammatory markers C-reactive protein (r = 0.65, P < 0.0001) and interleukin 6 (r = 0.62, P < 0.0001), and antioxidant blood compounds total bilirubin (r = 0.37, P < 0.001) and albumin (r = -0.54, P < 0.0001). Peroxiredoxin 4 distinguished noninfectious from infectious inflammatory response syndrome with an area under the receiver operating characteristic (ROC) curve of 0.82. [corrected] High Prx4 serum levels were associated with a poor prognosis of septic patients and revealed an area under the ROC curve of 0.76 in prediction of in-hospital mortality. In this study, elevated serum levels of the antioxidant Prx4 were associated with an increased disease severity and adverse outcome of critically ill patients with sepsis. Peroxiredoxin 4 may therefore be a helpful new biomarker for diagnosing, monitoring, and risk assessing these patients. The pathophysiological mechanisms behind the observed increase remain to be elucidated.
氧化应激是一种活性氧（ROS）产生增加和/或抗氧化防御机制减少的情况，在脓毒症的发病机制中很明显。过氧化物酶 4（Prx4）是一种新近在脓毒症患者的循环血液中发现的过氧化氢降解过氧化物酶，可能反映了失衡的抗氧化系统。我们研究了 79 名连续入组的重症监护病房患者的 Prx4 血清水平。Prx4 的诊断和预后性能与其他生物标志物、APACHE II 评分和 SOFA 评分进行了比较。入院时被诊断为全身炎症反应综合征（2.32 个任意单位[arb.]/L）、脓毒症（5.02 arb. U/L）、严重脓毒症（11.7 arb. U/L）或脓毒性休克（11.4 arb. U/L）的患者，其 Prx4 血清水平逐渐随疾病严重程度升高。Prx4 与严重程度评分急性生理和慢性健康评估 II（r = 0.27，P < 0.05）和器官衰竭评分序贯器官衰竭评估（r = 0.55，P < 0.0001）呈正相关。Prx4 与脓毒症标志物降钙素原（r = 0.61，P < 0.0001）、炎症标志物 C 反应蛋白（r = 0.65，P < 0.0001）和白细胞介素 6（r = 0.62，P < 0.0001）以及抗氧化血化合物总胆红素（r = 0.37，P < 0.001）和白蛋白（r = -0.54，P < 0.0001）呈正相关。Prx4 区分了非传染性和传染性炎症反应综合征，ROC 曲线下面积为 0.82。高 Prx4 血清水平与脓毒症患者的不良预后相关，预测住院死亡率的 ROC 曲线下面积为 0.76。在这项研究中，抗氧化 Prx4 血清水平升高与危重患者脓毒症严重程度增加和不良预后相关。因此，Prx4 可能是诊断、监测和评估这些患者风险的一种有用的新型生物标志物。观察到的增加背后的病理生理机制仍有待阐明。
