Circulating autoantibody and intrahepatic inflammation profiles in patients chronically infected with hepatitis C virus (P6328)

Abstract

Abstract The liver injury in hepatitis C virus (HCV) infection is thought to be mainly due to immunological disorders and attacks of inflammatory factors rather than a direct cytopathic effect of the virus itself. To investigate whether intrahepatic inflammation and immunological disorders are correlated in HCV-infected patients, we used a real-time RT-PCR-based array and a slide-based autoantigen array to analyze intrahepatic inflammation gene profiles in liver biopsy specimens from HCV-infected (n=16) and uninfected (n=8) individuals and their circulating autoantibody profiles, respectively. Compared with uninfected individuals, HCV infection markedly altered expression of 59.5% of 84 inflammation-related genes tested. Among these genes affected, the CXCR3-associated chemokines (CXCL9, CXCL10, and CXCL11) were among the most up-regulated genes. Patients chronically infected with HCV have 2-fold or greater increase in circulating autoantibodies of IgG and IgM to 28 and 23 of 84 autoantigens tested, respectively, than that in uninfected individuals. The antinuclear antibody IgG titers correlated significantly with the levels of intrahepatic CXCR3-associated chemokines (p = 0.002). Given that CXCR3-associated chemokines are involved in the development of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), these chemokines may also play a key role in the pathogenesis of HCV-related liver disease through enhancement of autoimmune responses.