Is primary biliary cirrhosis an autoimmune disease?

This review summarizes the experimental and clinical support for an autoimmune origin of primary biliary cirrhosis (PBC). Direct proof is lacking, but indications in favour of an immunologic destructive mechanism include the demonstration of antibodies and T cell clones with specificity for mitochondrial autoantigens, and the lymphocytic infiltration/destruction of small bile ducts similar to that of graft-vs-host disease and rejection. There is a weak association with other autoimmune diseases, but no clear HLA linkage. Spontaneous animal models for PBC are lacking, and immunization of animals with purified autoantigen does not result in typical disease. Anti-mitochondrial antibodies (AMAs) of M2 type are diagnostic of PBC, and are mainly directed against a functional, restricted epitope on the E2 subunit of the pyruvate dehydrogenase complex (PDC). PDC-E2 shows several similarities to other classical autoantigens. The pathogenic role of AMA remains elusive. Recent studies have shown that AMAs detect an antigenic epitope expressed on the luminal surface of biliary epithelium in PBC liver. The initial triggering event might represent a microbial infection (molecular mimicry), or an aberrant surface expression of a true autoepitope.