Semenov A V, Arsentieva N A, Lubimova N E, Tulienev S V, Basina V V, Esaulenko E V, Totolyan A A
Klin Lab Diagn. 2015 Aug;60(8):45-51.
The chronic viral hepatitis C is widely prevalent disease with prolonged persistence of virus and obliterated clinical picture. The present techniques of diagnostic of degree of fibrosis of liver and prognosis of course of disease have particular shortcomings. Hence, search of safe low invasive methods based on blood biomarkers is an actual task. The cytokines/chemokines (mediators of chronic inflammation) directly involved into immunopathogenesis of chronic viral hepatitis C can act in the capacity of biomarkers. The study was carried out to comprehensively analyze content of cytokines/chemokines in peripheral blood of patients with chronic viral hepatitis C at various stages of disease and infected by different genotypes of virus of hepatitis C. The concentration of cytokines/chemokines was identified in blood plasma of patients with chronic viral hepatitis C (n = 73) and conditionally healthy donors (n =3 7): IFNα, IFNγ, IFNλ/IL28α, TNFα, CCL2/MCP-1, CCL3/MIP-lα, CCL4/MIP-lβ, CCL5/RANTES, CCL8/MCP-2, CCL20/AIP-3α, CXCL9/MIG, CXCL10/P-10, CXCLII/ITAC. The multiplex analysis using technology xMAP was applied. The increasing of level of TNFα, CCL2/MCP-1, CCL4/ MIP-l, CCL8/ACP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITA C was established in blood plasma of patients with chronic viral hepatitis C as compared with control group. The levels of analyzed interferons IFNα, IFNγ, IFNλ/IL28α had no difference in studied groups. As far as chronic viral hepatitis C progresses and fibrosis of hepatic tissue develops the concentrations of TNFα, CCL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-l0, CXCL11/ITAC increased significantly. The concentrations of chemokine CXCL11/IT4 C can be used as informative indicator for differentiating diagnostic of early stages of liver fibrosis. Depending on genotype of virus of hepatitis C, in patients with chronic viral hepatitis C change in content of CCL8/MCP-2 was established. Hence, detection in blood plasma of patients with chronic viral hepatitis C concentration of particular cytokines/chemokines using multiplex analysis technique permit analyzing additional information concerning degree of liver fibrosis, activity of process of damage of hepatic tissue under chronic viral hepatitis C that indicates indirectly on genotype of virus of hepatitis C.
慢性丙型病毒性肝炎是一种广泛流行的疾病，病毒持续存在时间长，临床表现不明显。目前用于诊断肝纤维化程度和疾病进程预后的技术存在特定缺陷。因此，寻找基于血液生物标志物的安全、低侵入性方法是一项现实任务。细胞因子/趋化因子（慢性炎症介质）直接参与慢性丙型病毒性肝炎的免疫发病机制，可作为生物标志物。本研究旨在全面分析不同疾病阶段和感染不同丙型肝炎病毒基因型的慢性丙型病毒性肝炎患者外周血中细胞因子/趋化因子的含量。测定了73例慢性丙型病毒性肝炎患者和37例健康对照者血浆中细胞因子/趋化因子的浓度：IFNα、IFNγ、IFNλ/IL28α、TNFα、CCL2/MCP-1、CCL3/MIP-1α、CCL4/MIP-1β、CCL5/RANTES、CCL8/MCP-2、CCL20/MIP-3α、CXCL9/MIG、CXCL10/IP-10、CXCL11/ITAC。采用xMAP技术进行多重分析。结果发现，与对照组相比，慢性丙型病毒性肝炎患者血浆中TNFα、CCL2/MCP-1、CCL4/MIP-1、CCL8/ACP-2、CCL20/MIP-3α、CXCL9/MIG、CXCL10/IP-10、CXCL11/ITAC水平升高。所分析的干扰素IFNα、IFNγ、IFNλ/IL28α在研究组之间无差异。随着慢性丙型病毒性肝炎进展和肝组织纤维化发展，TNFα、CCL2/MCP-1、CCL20/MIP-3α、CXCL9/MIG、CXCL10/IP-10、CXCL11/ITAC浓度显著升高。趋化因子CXCL11/ITAC的浓度可作为肝纤维化早期鉴别诊断的信息指标。根据丙型肝炎病毒基因型，慢性丙型病毒性肝炎患者CCL8/MCP-2含量发生变化。因此，采用多重分析技术检测慢性丙型病毒性肝炎患者血浆中特定细胞因子/趋化因子的浓度，有助于分析有关肝纤维化程度、慢性丙型病毒性肝炎肝组织损伤过程活性的额外信息，间接提示丙型肝炎病毒基因型。
