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.