A contemporary perspective on the molecular characteristics of mitochondrial autoantigens and diagnosis in primary biliary cholangitis

ABSTRACT

Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disease characterized by immune mediated destruction of the intrahepatic small bile ducts and the presence of antimitochondrial antibodies (AMAs). The mitochondrial autoantigens have been identified as the E2 subunits of the 2-oxo-acid dehydrogenase complex, including the E2 subunits of pyruvate dehydrogenase, branched-chain 2-oxo acid dehydrogenase complex, oxoglutarate dehydrogenase complex, E3 binding protein and PDC E1 alpha subunit. The AMA epitope is mapped within the E2 lipoic acid binding domain, which is particularly important for oxidative phosphorylation. In addition, lipoic acid, which serves as a swinging arm to capture electrons, is particularly susceptible to an electrophilic attack and may provide clues to the etiology of PBC. This review emphasizes the molecular characteristics of AMAs, including detection, immunochemistry and the putative role in disease. These data have significance not only specifically for PBC, but generically for autoimmunity.

KEYWORDS:

• Antimitochondrial antibodies
• E2 subunit of pyruvate dehydrogenase (PDC-E2)
• indirect immunofluorescence
• immunoblotting
• ELISA
• Luminex bead assay
• enzyme inhibition assay

Acknowledgement

This work is supported in part by a National Institutes of Health grant DK39588 to ME Gershwin.

Financial & competing interests disclosure

PSC Leung and ME Gershwin have a United States patent (US6111071), ‘Recombinant Fusion Protein Comprising PDC-E2, BCOADC-E2 and OGDC-E2 and uses thereof’. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.