Hepatitis C virus infection and autoimmune diseases

Abstract

Hepatitis C virus (HCV) infection is associated with a number of extrahepatic disorders. The most studied conditions associated with HCV are type II mixed cryoglobulinemia and B cell lymphoma. However, many reports suggest that HCV might also be associated with a number of autoimmune disorders, both organ-specific and not organ-specific. Although concomitant treatment of HCV infection is a confounding factor when ascertaining the actual role of HCV in inducing autoimmune disease, a considerable amount of experimental data indicates that HCV is able to subvert the immune system and consequently induce autoimmunity. In the present review, we report a series of observations which associate chronic HCV infection with the onset of autoimmune disorders.

Keywords: autoimmune diseases; hepatitis C virus; immune regulation.

Figure 1

Possible mechanisms of autoimmunity induced by hepatitis C virus (HCV). Notes: HCV infects hepatocytes and interacts with B lymphocytes. HCV and hepatocyte-derived apoptotic proteins are taken up by tissue-resident dendritic cells, which mature and migrate into the draining lymph nodes. Here they activate naïve HCV-specific and self-peptide-specific T cells. These cells in turn differentiate into effector proinflammatory T helper-1, T helper-17, or cytotoxic T lymphocytes. Effector T cells can recognize either HCV-derived peptides on the hepatocyte surface or peptides self-expressed by noninfected cells, with the possible triggering of autoimmunity. Specific B cells are activated by T helper cells via CD40L/CD40 interaction and are induced to produce both anti-HCV and natural nonorgan-specific autoantibodies. These autoantibodies can react against components of self. Finally, HCV-specific T and B cells can recognize self-antigens by a mechanism of molecular mimicry between virus and host. Abbreviation: MHC, major histocompatibility complex.