Analysis of HCV‐Immunoglobulin Isotype Complexes Provide New Insights into Antibody Response to HCV

Abstract

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.

C3/Ig and Ig/C3 two-component-determined circulating immune complexes (TCIC) in patients with HCV infection

“…We have further shown that the levels of these TCIC are related to HCV infection and the degree of liver cell injury and that the changes in ALT level are associated with Ig isotypes. These findings are in accord with studies on the detection of conglutinin‐binding CIC and immuno‐capture reverse transcription polymerase chain reaction [2,8,9]. The accumulation supports that the pathogenic role of CIC in liver injury might be present, but more data, including studies in liver biopsies, are necessary to confirm the role.…”

“…The fact that the liver in patients with HCV does not work optimally for the concentrations of Igs and C3 results in the elevation of C3/IgG‐TCIC and the decrease of IgG/C3‐TCIC, suggesting a novel characteristic feature of HCV infection and suggesting that IgG immune complexes may be a major pathological factor. This feature cannot be characterized by earlier assays that we, or others, have reported [8–10,19–22]. Therefore, our method developed by reciprocal use of coating and detecting antibodies in this study is very helpful to further understand the component proportion and the role of CIC.…”

“…CIC have been thought a pathological factor in many diseases [9,22]. Their role in liver cell injury has been noted in patients with chronic HCV infection [2].…”

“…Furthermore, Tsai and colleagues [2] have characterized the profile of immunoglobulin (Ig) M‐ and IgG‐containing circulating immune complexes (CIC) using both C1q and conglutinin in an Ig‐specific solid‐phase enzyme immunoassay. Recently, we have found that HCV bound to antibody was a common feature of HC and the defective IgG in HCV‐CIC may contribute to long‐term viremia [8,9]. Based on these studies, it was believed that CIC might play a role in the pathogenesis of chronic HC.…”

Detection of IgM and IgG complexes provides new insight into immune regulation of patients with malignancies: A randomized controlled trial

“…The CIC of a class of Ig with another class of Ig (Ig-Ig), or a class of Ig with C3 (Ig-C) is collectively referred to as two-component-determined CIC (TCIC), which may be detected by ELISA [2][3][4]. Unlike Ig-antigen (Ig-pathogen) and antigencomplement TCIC, which are constituted by an antigen and one of host Ig and complement [5][6][7][8][9], Ig-Ig and Ig-C TCIC are marked by two host components of Ig or/and complement and are a better marker for an understanding International Immunopharmacology 7 (2007) 1433 -1441 www.elsevier.com/locate/intimp of host immune status [2][3][4]. Our previous reports indicated that decreased frequency in gastric cancer and increased frequency in hepatitis A and Graves' disease form a peculiar trait for detection of IgM/IgG-TCIC and IgG/IgA-TCIC, suggesting that Ig/Ig-TCIC may be a hallmark for evaluation of host immune regulation [2].…”