Talaya Alberto, Solano Carlos, Giménez Estela, García Giménez José Luis, Vinuesa Víctor, Alberola Juan, Pallardó Federico V, Navarro David
Microbiology Service, Hospital Clínico Universitario, Institute for Research INCLIVA, Valencia, Spain.
Hematology Service, Hospital Clínico Universitario, Institute for Research INCLIVA, Valencia, Spain.
J Gen Virol. 2017 Jul;98(7):1855-1863. doi: 10.1099/jgv.0.000838. Epub 2017 Jul 10.
The level of antioxidants, such as thiol-containing tripeptide glutathione (GSH), in cytomegalovirus (CMV)-infected cells is notably increased. We previously showed that GSH levels in plasma, as measured by untargeted 1H nuclear magnetic resonance, are higher in allogeneic stem cell transplant (allo-SCT) recipients who subsequently develop CMV viraemia. We hypothesized that the net level of oxidative-stress markers present in plasma may be reduced in patients who develop CMV DNAaemia compared to those who do not. We serially monitored the levels of malondialdehyde (MDA) and carbonylated proteins (CPs) early after allo-SCT and assessed whether they could predict the occurrence of CMV DNAaemia. MDA levels were measured in 43 patients (28 had CMV DNAaemia) and CPs were quantified in 53 patients (38 patients developed CMV DNAaemia). The area under the curve (AUC) value for MDA, but not for CPs, was significantly lower in patients who subsequently developed CMV DNAaemia compared to those who remained DNAaemia-free (P=0.043). A trend toward lower MDA AUC values was observed in episodes of CMV DNAaemia with faster CMV replicative kinetics and in those who reached higher peak CMV DNA levels. Moreover, receiver operating characteristic curve analyses indicated that the MDA biomarker had the predictive ability to discriminate between patients with or without subsequent CMV DNAaemia (AUC=0.69, 95 % confidence interval 0.51-0.85, P=0.05). In summary, serial quantitation of MDA may be useful for individualizing antiviral prophylaxis therapies (targeted prophylaxis) in the upcoming era of new antiviral drugs with improved safety profiles.
巨细胞病毒（CMV）感染细胞中抗氧化剂的水平，如含硫醇的三肽谷胱甘肽（GSH），显著升高。我们之前表明，通过非靶向1H核磁共振测量，在随后发生CMV病毒血症的异基因干细胞移植（allo-SCT）受者中，血浆中的GSH水平更高。我们推测，与未发生CMV DNA血症的患者相比，发生CMV DNA血症的患者血浆中氧化应激标志物的净水平可能会降低。我们在allo-SCT后早期连续监测丙二醛（MDA）和羰基化蛋白（CPs）的水平，并评估它们是否可以预测CMV DNA血症的发生。在43例患者中测量了MDA水平（28例发生CMV DNA血症），在53例患者中对CPs进行了定量（38例患者发生CMV DNA血症）。与未发生DNA血症的患者相比，随后发生CMV DNA血症的患者中，MDA的曲线下面积（AUC）值显著更低，但CPs的AUC值并非如此（P = 0.043）。在CMV复制动力学较快且达到较高CMV DNA峰值水平的CMV DNA血症发作中，观察到MDA AUC值有降低的趋势。此外，受试者工作特征曲线分析表明，MDA生物标志物具有区分后续发生或未发生CMV DNA血症患者的预测能力（AUC = 0.69，95%置信区间0.51 - 0.85，P = 0.05）。总之，在具有更好安全性的新型抗病毒药物即将到来的时代，连续定量MDA可能有助于个性化抗病毒预防治疗（靶向预防）。
