Molecular characterization of autoantigens in autoimmune liver diseases

摘要

The diagnosis of the autoimmune liver diseases primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) is reached by exclusion of other causes of chronic hepatic damage which include viral infection, metabolic abnormalities, genetic liver diseases and toxic exposure, as well as haemodynamic alterations. One of the most striking features of AIH and PBC is the elevation of serum immunoglobulin levels and the detection of circulating autoantibodies. A third presumably (auto)immune-mediated condition of the liver is primary sclerosing cholangitis, which is not characterized by female predominance, a well-defined autoantibody/autoantigen profile or a response to immunosuppression. The majority of research has focused on the characterization of autoantibodies associated with PBC and AIH, From a clinical point of view these two diseases differ in their classical biochemical presentation, AIH displaying a typical 'hepatitic' enzyme profile with elevated alanine aminotransferase (ALT) > aspartate aminotransferase (AST) in addition to an elevation of immunoglobulin G levels, and PBC displaying a typical cholestatic profile with an elevation of alkaline phosphatase (AP) and gamma-glutamyltransferase (7-GT), as well as bilirubin. However, autoantibody profiles in both diseases are both distinguishing and characterized by a degree of overlap: PBC displays antimitochondrial autoantibodies (AMA) which are neither organ- nor cell type-specific, in addition to antinuclear autoantibodies (ANA) which are neither cell- nor disease-specific.