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

Abstract

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.