Autoantigens in primary biliary cirrhosis

The automimmune liver disease primary biliary cirrhosis (PBC) is characteri sed by serum autoantibodies directed at mitochondrial and nuclear antigens (seen in most patients and a subset of patients, respectively). The antimit ochondrial antibodies (AMA) characteristic of PBC are directed at members o f the 2-oxoacid dehydrogenase components of multienzyme complexes; in parti cular, the E2 and E3 binding protein (E3BP) components of the pyruvate dehy drogenase complex (PDC). The presence of autoantibodies reactive with PDC-E 2 and/or E3BP is strongly predictive of the presence of PBC. Therefore, the detection of these antibodies plays a very important role in the diagnosis of PBC. Originally demonstrated using immunofluorescence approaches, AMA c an now be detected by the use of commercially available enzyme linked immun osorbent assays (ELISAs). Although the ELISA based approaches have advantag es in terms of laboratory practicality, they are slightly less sensitive fo r the diagnosis of PBC than immunofluorescence (occasional patients with PB C show reactivity with PDC related antigens not present in the antigen prep arations available for use with ELISA). Therefore, immunofluorescence shoul d continue to be available as a complementary diagnostic test for use in oc casional patients. In a subset of patients with PBC, autoantibodies are dir ected at increasingly well characterised nuclear antigens. Antinuclear anti body (ANA) positive patients are typically ARIA negative. There are no sign ificant differences in disease phenotype between AMA positive and AMA negat ive groups. At present, the clinical detection of ANA is mostly by Hep2 imm unofluorescence, although ELISA kits for individual nuclear antigens are in creasingly becoming available.