Abstract
Primary Biliary Cirrhosis (PBC) is considered an autoimmune disease characterized by immune-mediated destruction of the intrahepatic bile ducts and its characteristic serologic marker, the anti-mitochondrial antibody (AMA). Several factors were proposed to clarify the pathological and immunological mechanisms of PBC. Immunological reaction with a bacterial or a viral association was identified in the previous report, and it seems probable that PBC was thought to have such an etiology. The majority of patients with PBC was reported to have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes or in 2008, the patient who developed PBC with high HIV viral load had an antiviral therapy and recovered. To understand the etiology of PBC associated with infection, several factors should be considered and especially animal models may be useful. In this paper, we introduce three typical animal models of PBC: the dominant-negative form of transforming growth factor-β receptor type II (dnTGFβRII) mouse, IL-2Rα −/− mouse and NOD.c3c4 mouse, are enumerated and described, and we discuss previous reports of viral infection associated with PBC and consider the etiology of PBC from our analysis of results in NOD.c3c4 mouse.
Highlights
Primary Biliary Cirrhosis (PBC) is considered an autoimmune disease characterized by immune-mediated destruction of the intrahepatic bile ducts and its characteristic serologic marker, the anti-mitochondrial antibody (AMA)
AMA is a highly specific autoantibody found in about 90% of patients with PBC that reacts with an epitope on the E2 subunit of the pyruvate dehydrogenase enzyme complex (PDCE2) [1,2,3]
The epitopes discerned by anti-PDC-E2 and CD4 and CD8 autoreactive T cells are present in the inner lipoyl domain of PDC-E2
Summary
Primary Biliary Cirrhosis (PBC) is considered an autoimmune disease characterized by immune-mediated destruction of the intrahepatic bile ducts and its characteristic serologic marker, the anti-mitochondrial antibody (AMA). The mechanism to explain the association of infection is molecular mimicry of autoepitops by peptides of microorganisms. This results in cryptic T-cell epitopes, the degeneracy of T-cell receptors, and the disruption of immune tolerance [15, 16]. There are several mechanisms by which viruses are thought to induce an autoimmune response. These include the expression of some autoantigens, the expression of major histocompatibility complex molecules, and changes in cytokine production [16]. We discuss previous reports of viral infection associated with PBC and consider the etiology of PBC from our analysis of results in NOD.c3c4 mouse
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