Guler Nil, Eroglu Cafer, Yilmaz Hava, Karadag Adil, Alacam Hasan, Sunbul Mustafa, Fletcher Tom E, Leblebicioglu Hakan
Department of Hematology, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
Department of Clinical Microbiology and Infectious Diseases, School of Medicine, Ondokuz Mayis University, Samsun, Turkey.
PLoS One. 2016 Jun 15;11(6):e0157247. doi: 10.1371/journal.pone.0157247. eCollection 2016.
Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended.
克里米亚-刚果出血热（CCHF）是一种危及生命的急性病毒感染，其特征为发热、出血、白细胞减少和血小板减少。它是一种主要的新出现的传染病威胁，但其发病机制仍知之甚少，关于细胞凋亡在急性感染中的作用的数据也很少。我们旨在通过一项针对成年CCHF患者的横断面队列研究，评估白细胞中凋亡基因的表达。在土耳其的一家三级CCHF治疗单位招募了20名CCHF患者和10名健康对照；入院时采集基线血液检测样本并分离总RNA。使用实时定量人凋亡基因检测试剂盒进行实时PCR，检测基因表达差异。参与者有CCHF严重程度分级评分（SGS），其中10名低风险评分（20名中的10名）和10名中高风险评分（20名中的10名）的患者有死亡风险。20名参与者中有5人死亡。基因表达分析显示，CCHF患者组中促凋亡和抗凋亡基因的表达受到调节，从而促进细胞凋亡。观察到主要与TNF家族成员相关的显性外源性途径激活。严重和致命病例提示存在额外的内源性途径激活。相对基因表达的临床意义尚不清楚，建议进行更大规模的纵向研究，同时测量宿主和病毒因素。
