Association of the Sialylation of Antibodies Specific to the HCV E2 Envelope Glycoprotein with Hepatic Fibrosis Progression and Antiviral Therapy Efficacy.

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.

The Thomsen-Friedenreich Antigen-Specific Antibody Signatures in Patients with Breast Cancer.

Alterations in the glycosylation of serum total immunoglobulins show these antibodies to have a diagnostic potential for cancer but the disease-related Abs to the tumor-associated antigens, including glycans, have still poorly been investigated in this respect. We analysed serum samples from patients with breast carcinoma (n = 196) and controls (n = 64) for the level of Thomsen-Friedenreich (TF) antigen-specific antibody isotypes, their sialylation, interrelationships, and the avidity by using ELISA with the synthetic TF-polyacrylamide conjugate as an antigen and the sialic acid-specific Sambucus nigra agglutinin (SNA) and ammonium thiocyanate as a chaotrope. An increased sialylation of IgG and IgM, but a lower SNA reactivity of IgA TF antibodies, and a higher level and avidity of the TF-specific IgA were found in cancer patients. Other cancer-related signatures were the highly significant increase of the IgG/IgA ratio and the very low SNA/IgA index in cancer, including patients with an early stage of the disease. These changes showed a good diagnostic potential with about 80% accuracy. Thus, the level of naturally occurring anti-TF antigen antibodies, their sialylation profile, isotype distribution, and avidity displayed cancer-specific changes that could serve as novel noninvasive Ab-based biomarkers for early breast cancer.