Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Karadeniz Technical University, 61080, Trabzon, Turkey.
Int J Infect Dis. 2013 Nov;17(11):e1056-9. doi: 10.1016/j.ijid.2013.04.004. Epub 2013 Jun 3.
The purpose of this study was to investigate serum levels of serum urokinase plasminogen activation receptor (suPAR) during the first week of febrile neutropenia and to demonstrate the significance of this biomarker in the diagnosis and follow-up of febrile neutropenic patients with hematologic malignancies.
The study was performed between January 2011 and January 2012 at Karadeniz Technical University, Turkey. For neutropenic patients with hematologic malignancies, the day before the onset of fever and the first day of the febrile neutropenia attack were taken as days 0 and 1, respectively. Blood samples were obtained from patients with hematologic malignancies on days 0, 1, 3, 5, and 7. Sixty-eight healthy volunteers were enrolled as the control group. suPAR levels were determined using an ELISA kit following the manufacturer's protocols. Twenty-six male and 14 female patients with hematologic malignancies, the majority with acute/myeloid/lymphocytic leukemia, aged 19-78 years (mean 46.8 years), were included. Fifty febrile neutropenic attacks were investigated in these patients.
The mean serum levels of the controls and suPAR 0 were 3.9 ± 1.5 ng/ml and 5.8 ± 2.7 ng/ml, respectively. Serum levels of suPAR rose earlier than levels of C-reactive protein and procalcitonin. Serum suPAR levels increased in patients with hematologic malignancies and were found to represent an important serum biomarker for the early prediction of neutropenic fever. A decrease in serum suPAR levels was found to be correlated with treatment response due to antibiotics in this patient group. There were significant differences in suPAR 1 levels between patients with documented infection and those with fever of unknown origin in favor of the former. When the suPAR 1 results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 5.87 ng/ml, the area underneath the ROC curve (AUC) was 0.81 (95% confidence interval 0.68-0.91), sensitivity was 100%, specificity was 69%, negative predictive value (NPV) was 100%, and positive predictive value (PPV) was 70%.
We conclude that suPAR is an important biomarker that can predict infections in the early stage of febrile neutropenia with high sensitivity and NPV for patients with hematologic malignancies. It is also advantageous since it shows the response to treatment with antibiotherapy in the early stage.
本研究旨在探讨发热性中性粒细胞减少症第 1 周时血清尿激酶型纤溶酶原激活物受体（suPAR）的水平，并证明该生物标志物在血液病发热性中性粒细胞减少患者的诊断和随访中的意义。
本研究于 2011 年 1 月至 2012 年 1 月在土耳其的卡拉德尼兹技术大学进行。对于血液病中性粒细胞减少症患者，发热前一天和发热性中性粒细胞减少症发作的第 1 天分别为第 0 天和第 1 天。在第 0 天、第 1 天、第 3 天、第 5 天和第 7 天采集血液病患者的血液样本。68 名健康志愿者作为对照组入组。采用 ELISA 试剂盒按照制造商的方案测定 suPAR 水平。纳入了 26 名男性和 14 名女性血液病患者，其中大多数为急性/髓样/淋巴细胞白血病患者，年龄 19-78 岁（平均 46.8 岁）。这些患者共发生 50 次发热性中性粒细胞减少发作。
对照组和 suPAR0 的平均血清水平分别为 3.9±1.5ng/ml 和 5.8±2.7ng/ml。suPAR 水平早于 C 反应蛋白和降钙素原升高。血液病患者的血清 suPAR 水平升高，代表中性粒细胞减少性发热早期预测的重要血清生物标志物。在该患者组中，由于抗生素治疗，发现血清 suPAR 水平下降与治疗反应相关。在有明确感染的患者与发热原因不明的患者之间，suPAR1 水平存在显著差异，前者更高。使用接收器工作特征（ROC）曲线法分析 suPAR1 结果时，最佳诊断截断点为 5.87ng/ml，ROC 曲线下面积（AUC）为 0.81（95%置信区间 0.68-0.91），敏感性为 100%，特异性为 69%，阴性预测值（NPV）为 100%，阳性预测值（PPV）为 70%。
我们得出结论，suPAR 是一种重要的生物标志物，可在血液病发热性中性粒细胞减少症的早期阶段以高敏感性和 NPV 预测感染，并且由于其在早期显示出对抗生素治疗的反应，因此具有优势。
