Affiliations: The Zabludowicz Center for Autoimmune Diseases and
Department of Medicine B, Sheba Medical Center, Tel-Aviv, Israel | Tel-Aviv University, Tel-Aviv, Israel
Note: [] Corresponding author: Prof. Yehuda Shoenfeld, Head, Department
of Medicine B, Chaim Sheba Medical Center. Tel Hashomer 52621, Israel. Tel.:
+972 3 530 2652; Fax: +972 3 535 2855; E-mail: [email protected]
Abstract: Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic
liver disease which is characterized by the breakdown of self-tolerance to the
highly conserved pyruvate dehydrogenase complex, specially the pyruvate
dehydrogenase E2 complex (PDC-E2). The breakdown of the tolerance to such
antigens leads to an autoimmune process characterized by portal inflammation
and immune-mediated destruction of the intrahepatic bile ducts. Epidemiological
studies have suggested that infections agents can trigger or even exacerbate
the disease. Among other gram negative bacteria, Escherichia Coli, and
Nosphingobium aromaticivorans are the most associated agents reported
hitherto. Epidemiological and molecular evidence points towards molecular
mimicry between some components of these microorganisms and specific amino-acid
sequences that are present in proteins on normal cells of the biliary tract. In
this review, we revisit all reports suggesting that infectious agents might be
associated with the autoimmune pathogenesis of PBC. We also retrieve the immune
molecular mimicry mechanisms that are likely involved with the autoimmune
process in PBC.
