HCV E2糖蛋白特异性和天然抗聚糖(TF, αGal)抗体的唾液酰化作为肝损伤的标志

O. Kurtenkov, J. Jakovleva, B. Sergejev, J. Geller
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摘要

E2糖蛋白是抗丙型肝炎病毒(HCV)广泛中和抗体的靶标。有证据表明,HCV e2特异性抗体糖基化谱与肝纤维化进展有关。本研究的主要目的是比较e2特异性和天然存在的抗糖多糖抗体的唾液化,以确定它们的组合是否有益于肝损伤的非侵入性评估。对58例不同阶段肝纤维化或无肝纤维化的患者进行了检测。采用ELISA平台分析HCV E2糖蛋白特异性抗体(E2- abs)、Thomsen-Friedenreich抗原和αGal糖基特异性抗体(TF-Abs、αGal- abs)的唾液酰化水平。根据肝纤维化分期、HCV基因型及抗病毒治疗效果,测定血清IgG抗体水平及对唾液特异性黑参凝集素(SNA)的反应性,分析抗体唾液化水平的变化。晚期肝纤维化(F4)与无纤维化期(P=0.003)和F1-F3期(P=0.0007)不同,E2-Ab SNA反应性显著降低。相反,抗多糖抗体显示唾液化增加。在多元回归分析中,E2和TF-Abs唾液化模式的结合在评估肝损伤方面具有显著优势。F0期和F4期以及F1-F3期和F4期的鉴别率较高(ACC=0.948, ACC=0.90)。因此,结合疾病特异性和天然抗体唾液化分析,可以显著提高该方法在无创肝损害评估中的临床价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sialylation of HCV E2 Glycoprotein-Specific and Natural Anti-Glycan (TF, αGal) Antibodies as Signatures of Liver Damage
The E2 glycoprotein is the target of broadly neutralizing antibodies against Hepatitis C Virus (HCV). There is evidence that the HCV E2-specific antibody glycosylation profile is associated with hepatic fibrosis progression. The main aim of this study was to compare the sialylation of E2-specific and naturally occurring antiglycan Abs to determine whether their combination could be beneficial for the non-invasive evaluation of hepatic damage. Fifty-eight patients with various stages of hepatic fibrosis or without were tested. The sialylation of HCV E2 glycoprotein-specific antibodies (E2-Abs), the Thomsen-Friedenreich antigen- and αGal glycotope-specific antibodies (TF-Abs, αGal-Abs) was analysed using the ELISA platform. The level of IgG Abs and their reactivity to Sialospecific Sambucus Nigra Lectin (SNA) were determined and changes in Abs sialylation were analysed based on the stage of liver fibrosis, HCV genotype and antiviral therapy efficacy. The late stage of liver Fibrosis (F4) was characterized by dramatically decreased E2-Ab SNA reactivity unlike stages with no fibrosis (P=0.003) and stages F1–F3 (P=0.0007). In contrast, antiglycan Abs showed an increased sialylation. In multiple regression analysis, the combination of E2 and TF-Abs sialylation patterns gave a significant advantage in assessing liver damage. A high rate of discrimination between F0 and F4 stages of fibrosis as well as between F1–F3 and F4 was obtained (ACC=0.948 and ACC=0.90, respectively). Thus, the combined analysis of disease-specific and natural Abs sialylation can remarkably enhance the clinical value of the approach in the non-invasive evaluation of hepatic damage.
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