Autoantigens in primary biliary cirrhosis

Abstract

The automimmune liver disease primary biliary cirrhosis (PBC) is characterised by serum autoantibodies directed at mitochondrial and nuclear antigens (seen in most patients and a subset of patients, respectively). The antimitochondrial antibodies (AMA) characteristic of PBC are directed at members of the 2-oxoacid dehydrogenase components of multienzyme complexes; in particular, the E2 and E3 binding protein (E3BP) components of the pyruvate dehydrogenase complex (PDC). The presence of autoantibodies reactive with PDC-E2 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 can now be detected by the use of commercially available enzyme linked immunosorbent assays (ELISAs). Although the ELISA based approaches have advantages in terms of laboratory practicality, they are slightly less sensitive for the diagnosis of PBC than immunofluorescence (occasional patients with PBC show reactivity with PDC related antigens not present in the antigen preparations available for use with ELISA). Therefore, immunofluorescence should continue to be available as a complementary diagnostic test for use in occasional patients. In a subset of patients with PBC, autoantibodies are directed at increasingly well characterised nuclear antigens. Antinuclear antibody (ANA) positive patients are typically AMA negative. There are no significant diVerences in disease phenotype between AMA positive and AMA negative groups. At present, the clinical detection of ANA is mostly by Hep2 immunofluorescence, although ELISA kits for individual nuclear antigens are increasingly becoming available. (J Clin Pathol 2000;53:813-821)

Resistance to activation-induced cell death and elevated FLIPL expression of CD4+ T cells in a polyI:C-induced primary biliary cirrhosis mouse model

“…Primary biliary cirrhosis is a kind of autoimmune disease caused by the impairment of the host's immune tolerance to its mitochondrial antigen by an as yet undetermined mechanism [12]. We established a PBC animal model by injecting C57BL/6 mice with polyI:C and found that AICD in splenic and hepatic CD4?…”

Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosis

“…The major mitochondrial antigens reacting with AMA have been identified as components of the 2-oxoacid (or a-ketoacid) dehydrogenase complexes contain pyruvate dehydrogenase (PDH), branch chain 2-oxo acid dehydrogenase (BCOADH), 2-oxoglutarate dehydrogenase (OGDH), and protein X, each of which contains multiple copies of catalytic components that catalyze the consecutive steps in the oxidative decarboxylation of 2-oxo acid substrates. PBC sera also recognize other liver antigens: centromere antigens and multiple antinuclear ''nuclear dots'' antigen (3)(4)(5).…”

Association of Primary Biliary Cirrhosis-autoimmune Hepatitis Overlap Syndrome with Immune Thrombocytopenia and Graves' Disease

“…PBC is characterized by progressive inflammatory damage to the biliary epithelial cells, elevated biliary tract enzymes and positive anti-mitochondrial antibody (AMA). PBC is known to frequently have other autoimmune phenomena (3,4). Anti-platelet autoantibodies are detected in approximately 40% of patients and it is assumed that the immune-mediated destruction of platelets contributes to the thrombocytopenia in a considerable portion of patients with PBC (5,6).…”