Singh Nina, Inoue Makoto, Osawa Ryosuke, Wagener Marilyn M, Shinohara Mari L
Department of Medicine, Division of Infectious Diseases, VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, PA, United States.
Department of Immunology, Duke University School of Medicine, Durham, NC, United States.
J Clin Virol. 2017 Aug;93:8-14. doi: 10.1016/j.jcv.2017.05.012. Epub 2017 May 18.
CMV viremia is a contributor to poor outcomes in critically ill patients with sepsis.
To assess the expression levels of genes encoding inflammasome-related proteins in the development of CMV viremia in critically ill patients with sepsis.
A cohort of CMV-seropositive critically ill patients with sepsis due to bloodstream infection underwent weekly testing for CMV viremia. Blood samples to evaluate mRNA levels of genes encoding CASP1, ASC, NLRP1, NLRP3, and NLRP12 were collected at the time of enrollment. Clinical outcomes were assessed at 30days or until death/discharge from ICU.
CMV viremia was documented in 27.5% (8/29) of the patients, a median of 7days after the onset of bacteremia. Patients with sepsis who developed CMV viremia had higher CASP1 although this was not statistically significant (relative mean 3.6 vs 1.8, p=0.13). Development of high grade CMV viremia however, was significantly associated with CASP1; septic patients who developed high grade CMV viremia had significantly higher CASP1than all other patients (relative mean 5.5 vs 1.8, p=0.016).
These data document possible involvement of inflammasome in the pathogenesis of CMV. Regulating the host immune response by agents that target these genes may have implications for improving CMV-related outcomes in these patients.
巨细胞病毒血症是导致脓毒症重症患者预后不良的一个因素。
评估脓毒症重症患者巨细胞病毒血症发生过程中编码炎性小体相关蛋白的基因表达水平。
一组因血流感染导致脓毒症的巨细胞病毒血清学阳性重症患者每周接受巨细胞病毒血症检测。在入组时采集血样以评估编码半胱天冬酶 -1(CASP1)、凋亡相关斑点样蛋白(ASC)、核苷酸结合寡聚化结构域样受体含吡咯素结构域蛋白1(NLRP1)、核苷酸结合寡聚化结构域样受体含热蛋白结构域相关蛋白3(NLRP3)和核苷酸结合寡聚化结构域样受体含热蛋白结构域相关蛋白12(NLRP12)的基因的mRNA水平。在30天时或直至死亡/从重症监护病房出院时评估临床结局。
27.5%(8/29)的患者出现巨细胞病毒血症,发生时间中位数为菌血症发作后7天。发生巨细胞病毒血症的脓毒症患者的CASP1水平较高,尽管差异无统计学意义(相对均值3.6对1.8,p = 0.13)。然而,高等级巨细胞病毒血症的发生与CASP1显著相关;发生高等级巨细胞病毒血症的脓毒症患者的CASP1显著高于所有其他患者(相对均值5.5对1.8,p = 0.016)。
这些数据证明炎性小体可能参与了巨细胞病毒的发病机制。通过靶向这些基因的药物调节宿主免疫反应可能对改善这些患者的巨细胞病毒相关结局具有意义。