Differential humoral immune response against hepatitis C virus antigenic synthetic peptides in infected patients with and without mixed cryoglobulinaemia

In this study we have evaluated the prevalence of antibodies against core region peptides (residues 1–28, 21–38 and 51–68), the envelope 1, the non‐structural (NS) 4 and 5 proteins of hepatitis C virus (HCV) in sera from 65 chronically HCV‐infected patients, 47 with mixed cryoglobulinaemia (MC + ) and 18 without (MC − ). The major binding sites were located within the core region. Regions 1–28 and 51–68 were recognized by a similar proportion of MC + and MC − patients, while peptide 21–38 was less frequently detected by samples from MC + patients (65.5% versus 100%; P =0.011). The patterns of the reactions showed a minimum of three binding sites: one, located within region 51–68, was shared by both groups; a second determinant was identified at residues 1–21 for MC + patients and at residues 28–38 for MC − patients; a third, not exactly localized, lay between residues 1 and 38. Recognition of NS5 peptides was not significantly different between MC + and MC − patients, but while the former mostly reacted either with peptide 1 (residues 2294–2309) (five of 15 sera) or with peptide 2 (residues 2304–2319) (nine of 15 sera), the latter group showed a more scattered reaction. Antibodies to HCV peptides prevalently belonged to IgG1 subclass. However, whereas IgG1 antibodies against peptide 21–38 and peptide 1 of NS5 were more frequently found in MC − rather than in MC + patients (100% versus 63.8%, P =0.003, and 22.2% versus 4.2%, P =0.025, respectively), IgG3 antibodies against region 1–28 were more frequent in MC + patients (53.19% versus 16.6%, P =0.0078). Overall, the data suggest that a differential humoral immune response to HCV antigens occurs in patients with and without cryoglobulinaemia.