Analysis of HCV-immunoglobulin isotype complexes provide new insights into antibody response to HCV

Hepatitis C virus (HCV) is known for its ability to establish persistent infection and cause chronic hepatitis in most infected individuals. The antibody response to HCV in HCV-circulating immune complexes (CIC) is unknown. In the present study, we have characterized distinct changes in patterns of HCV-immunoglobulin (Ig) constituents with disease category, viral mutation and clinical markers. The number of samples positive for single HCV-Ig, HCV-IgG and HCV-IgA, HCV-IgM and HCV-IgA, HCV-IgM and HCV-IgG, HCV-IgM, HCV-IgG and HCV-IgA in 47 samples tested were 8 (17%), 1 (2.1%), 9 (19.1%), 4 (8.5%) and 17 (36.2%), respectively. The occurrence of HCV-IgM and HCV-IgA in combination of two isotypes of HCV-Ig became predominant. These results show that defective IgG in HCV-CIC may contribute to long-term viremia. Further analysis indicated that the frequency of HCV RNA/IgA-CIC in the abnormal aspartic aminotransferase (AST) group was significantly higher than that of the normal AST group, and HCV RNA/IgA-CIC frequency in the abnormal alanine aminotransferase (ALT) group was slightly higher than that in the normal ALT group. IgA complexes may reflect the damage degree of liver function during the course of HCV infection. We also found that there were more mutations in supernatant than in other constituents from single-strand conformation polymorphism (SSCP) analysis. Our results suggest that Ig-complexed virions and free virions may have different biological consequences, with the latter being elusive to immunological elimination. The findings in this study may provide some new insights into antibody response to HCV.