Significant autoimmune markers of autoimmune liver disorders: Current status

Abstract

AbstractChronic inflammatory liver diseases are classified as chronic active hepatitis (CAH) or primary biliary cirrhosis (PBC) on the basis of clinical and pathological criteria. Autoantibodies allow the distinction between autoimmune forms of CAH and virally induced forms, in particular CAH non‐A, non‐B. Three different subgroups of autoimmune‐type CAH have been defined so far. Classical autoimmune “lupoid” CAH is characterized by antinuclear antibodies (ANA) and liver‐membrane autoantibodies (LMA). Antibodies against a liver‐kidney‐microsomal antigen (LKM) are found in a small group of generally young patients and are associated with a progressive form of autoimmune CAH. The target antigen as defined by immunoblotting is a protein at 50 kilodaltons (KD), and it has been detected on phenobarbital‐inducible isoenzymes of cytochrome P‐450. The third subgroup, clinically similar to “lupoid” CAH, is characterized by antibodies against a soluble cytoplasmic liver antigen (anti‐SLA). These antibodies cannot be diagnosed by routine methods, i.e., immunofluorescence, but are only found by radioimmunoassay or enzyme immunoassay. In primary biliary cirrhosis (PBC) the immune reactions are directed against the intrahepatic bile ducts rather than hepatocytes. Antimitochondrial antibodies (AMA), traditionally diagnosed by immunofluorescence, are found in up to 100% of PBC patients. Complement‐fixation test, radioimmunoassay, and enzyme immunoassay allow the distinction of disease‐specific subtypes of AMA. Immunoblotting allows the characterization at the molecular level of two PBC‐specific AMA subtypes, anti‐p48 and anti‐p62. The latter corresponds to the anti‐M2 antibodies described previously. All these antibodies are important tools in the differential diagnosis of chronic inflammatory liver diseases. Patients with autoimmune‐type CAH benefit from immunosuppressive therapy, while those with virally induced CAH do not. The role of these autoantibodies in the pathogenesis of CAH or PBC is not known as yet, but they are sensitive and specific diagnostic markers.