The Glycodiversity of HCV E2 Glycoprotein-Specific Antibodies as a Signature of Hepatic Damage and Virotherapy Efficacy

Research Article

J Hepat Res. 2022; 7(1): 1046.

The Glycodiversity of HCV E2 Glycoprotein-Specific Antibodies as a Signature of Hepatic Damage and Virotherapy Efficacy

Kurtenkov O*, Jakovleva J, Sergejev B and Geller J

Department of Virology and Immunology, National Institute for Health Development, Hiiu 42, Tallinn, Estonia

*Corresponding author: Kurtenkov O, Department of Virology and Immunology, National Institute for Health Development, Hiiu 42, Tallinn 11619, Estonia

Received: March 10, 2022; Accepted: April 04, 2022; Published: April 11, 2022


The HCV E2 glycoprotein-specific Abs (E2-Ab) is an important factor in the host resistance to hepatitis C virus (HCV) infection. There is evidence that the E2-Ab sialylation is associated with liver damage and virotherapy efficacy. The aim of this study was to further profile the E2-Ab glycosylation. The fucosylation and sialylation of E2-Ab in one hundred six (HCV)-infected patients were tested using the lectin-based ELISA platform. Data were analyzed by the stage of hepatic fibrosis, HCV genotype and the response to IF-RBV virotherapy. The changes in the E2–Ab glycosylation were also evaluated by the receiver operator characteristic curve (ROC) and multiple regression analysis.

The E2-Ab reactivity to fucose-specific Aleuria aurantia lectin (AAL) and sialo-specific Sambucus nigra agglutinin (SNA) was decreased in the advanced stages of liver fibrosis. The SNA binding analysis was more informative in the discrimination of patients with advanced fibrosis compared to those with earlier fibrosis stages or no fibrosis group. No significant correlation between the reactivities of SNA and AAL lectins was established irrespective of HCV genotype. The patients infected with HCV 3a genotype showed an increased E2-Ab fucosylation, a lower E2-SNA/E2-AAL ratio and a better response to virotherapy. The association of the E2-SNA/E2-AAL ratio with virotherapy outcome was observed in patients infected with HCV 1b genotype. A better response to IF-RBV therapy was found in patients with a higher fucosylated E2 Abs and a lower E2-SNA/E2-AAL ratio. Thus the significance of E2 antibodies in the course of HCV hepatitis was demonstrated to be dependent on their glycosylation, the sialylation/fucosylation ratio, as well as on HCV genotype.

Keywords: E2-specific antibody; Ab glycosylation; HCV hepatitis; HCV genotypes; Virotherapy efficacy; Liver damage; Non-invasive markers


AAL: Aleuria Aurantia Lectin; ACC: Accuracy of ROC Analysis; E2-Ab: The Level of Antibodies to HCV E2 Glycoprotein; E2-AAL: The Level of AAL Binding to E2-Specific Antibodies; E2-SNA: The Level of SNA Binding to E2-Specific Antibodies; IF-RBV: Pegylated Interferon-α-2a Plus Ribavirin Therapy; NR: No Response; RL: Relapse; ROC: Receiver Operator Characteristics Curve Analysis; SNA: Sambucus Nigra Agglutinin; SNA/AAL ratio: E2-SNA Reactivity/E2-AAL Reactivity Ratio; SVR: Sustained Virologic Response; TF: The Thomsen--Friedenreich Antigen (Galα1-3Gal NAc-R); αGal: Xenogenic Alpha-Gal Glycotope (Galα1-3Galβ1- 4GlcNAc-R)


The E2 envelope glycoprotein of hepatitis C virus (HCV) acts as a receptor binding protein, being thus one of the main targets for broadly neutralizing antibodies against HCV [1-4]. The immune response to E2 is an important factor in the resistance to and a spontaneous cure of HCV infection [5-7].

The critical role of Fc-linked glycans for both the pro-inflammatory and anti-inflammatory effector functions of IgG is now well established [8-11]. The predominant carbohydrate structure found in the serum IgG is a complex-type, core fucosylated, biantennary N-glycan. An increase of the G0F (agalactosylated, asialylated and fucosylated) IgG glycoform is the most prominent change in a variety of chronic inflammatory and autoimmune diseases, thus promoting a proinflammatory state [8,9,12-14]. The core fucosylation of IgG N-glycans, in which fucose α1,6 is added to the protein-adjacent GlcNAc of N-glycans, directly impacts IgG ADCC activity [15,16]. The IgG glycovariants lacking branching fucose have an increased affinity for specific Fc gamma receptors.

Notable, when compared to the advances made in the glycoprofiling of total serum immunoglobulins, an analysis of disease-specific Abs, including E2-specific antibodies, has remained relatively understudied. We reported recently that the E2 Ab sialylation as defined by SNA lectin binding was significantly decreased in the terminal (F4) stages of hepatic fibrosis (F) [17], thus being a good marker of advanced liver fibrosis. Interestingly, HCV unrelated natural antiglycan (TF, αGal)-specific Abs demonstrated quite opposite fibrosis-related changes, i.e. an increased sialylation in stage F4, and the combination of E2-specific and natural antiglycan Abs using multiple regression analysis allowed us to get a very high accuracy degree (>90%) in the diagnosis of hepatic fibrosis progression [18].

In the present study, we investigated the fucosylation and sialylation of E2 Abs as well as their interrelationship (the E2-SNA/ E2-AAL ratio) in HCV infected patients. The data were analyzed for HCV genotype (GT), stage of hepatic fibrosis (F) and treatment outcome and the clinical significance of the findings was estimated.

Material and Methods


Serum samples were taken from 106 HCV infected treatmentnaïve patients: men 66 and women 40 of median age of 39 years (range 19-68). The HCV genotype-based characteristics of patients and the effect of antiviral therapy are presented in Table 1. The investigation was carried out in accordance with the ICH GCP Standards and approved by Tallinn Medical Research Ethics Committee, Estonia. A written informed consent was obtained from all patients.