The E2 envelope glycoprotein of the hepatitis C virus (HCV) is a major target of broadly neutralizing antibodies that are closely related to a spontaneous cure of HCV infection. There is still no data about the diversity of E2-specific antibodies (Abs) glycosylation. The aim of this study was to analyze the level and sialylation of E2 IgG Abs, the relation of the respective changes to hepatic fibrosis (F) progression and their possible association with the efficacy of interferon-α-2a plus ribavirin (IFN-RBV) antiviral therapy. One hundred three HCV infected treatment-naive patients were examined using ELISA with E2 recombinant protein as antigen and sialic acid-specific Sambucus nigra agglutinin. The efficacy of the IFN-RBV treatment of patients with HCV dominant 1b and 3a genotypes (GT) was evaluated. A significant decrease of E2 Abs sialylation in the late stages of fibrosis was found irrespective of HCV genotype. On this basis, the F4 stage of fibrosis can be discriminated from its F0 or F1-3 stage by an about 75-79% accuracy. HCV infection of 1b genotype is associated with the production of lower sialylated E2 Abs, a higher frequency of F4 stage fibrosis, and a worse response to antiviral therapy. The increased SNA reactivity of E2 Abs was observed in patients with a sustained virological response (SVR). The proportion of SVR responders was significantly higher among patients with 3a genotype. However, for both dominant HCV genotypes (3a and 1b), an increased sialylation of E2 IgG was associated with a higher rate of patients with sustained virological response to antiviral therapy. Thus, the association of alterations of anti-E2 IgG Abs sialylation with hepatic fibrosis stage, HCV genotype, and the efficacy of antiviral therapy enables using these changes as novel noninvasive predictive biomarkers. The clinical potential of these findings is discussed.

中文翻译：

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HCV E2包膜糖蛋白特异性抗体的唾液酸化与肝纤维化进展和抗病毒治疗功效的关联。

丙型肝炎病毒（HCV）的E2包膜糖蛋白是广泛中和与HCV感染自发治愈密切相关的抗体的主要目标。尚无关于E2特异性抗体（Abs）糖基化多样性的数据。这项研究的目的是分析E2 IgG Abs的水平和唾液酸化，各自变化与肝纤维化（F）进展的关系以及它们与干扰素-α疗效的可能关系-2a加利巴韦林（IFN-RBV）抗病毒治疗。使用E2重组蛋白作为抗原和唾液酸特异的黑接骨木凝集素，通过ELISA检测了103名未感染HCV的未治疗患者。评估了IFN-RBV治疗HCV显性1b和3a基因型（GT）患者的疗效。不论HCV基因型如何，在纤维化晚期，E2 Abs唾液酸化水平均显着降低。在此基础上，可以将纤维化的F4期与F0或F1-3期区分开，准确度约为75-79％。1b基因型的HCV感染与唾液酸化E2抗体水平降低，F4期纤维化发生频率增加以及对抗病毒治疗反应较差有关。在具有持续病毒学应答（SVR）的患者中观察到E2 Abs的SNA反应性增加。3a基因型患者中SVR反应者的比例明显更高。但是，对于两种主要的HCV基因型（3a和1b），E2 IgG唾液酸化水平的提高与对抗病毒治疗产生持续病毒学应答的患者发生率更高。因此，抗E2 IgG Abs唾液酸化的改变与肝纤维化分期，HCV基因型和抗病毒疗法的功效之间的关联使得能够将这些改变用作新型的非侵入性预测生物标记物。讨论了这些发现的临床潜力。抗E2 IgG Abs唾液酸化的改变与肝纤维化分期，HCV基因型和抗病毒疗法的疗效之间的相关性使我们可以将这些改变用作新型的非侵入性预测性生物标志物。讨论了这些发现的临床潜力。抗E2 IgG Abs唾液酸化的改变与肝纤维化分期，HCV基因型和抗病毒疗法的疗效之间的相关性使我们可以将这些改变用作新型的非侵入性预测性生物标志物。讨论了这些发现的临床潜力。