CHARACTERIZATION OF ANTIMITOCHONDRIAL ANTIBODIES IN HEALTHY-ADULTS

The detection of antimitochondrial antibodies (AMAs) is an important c riterion for the diagnosis of primary biliary cirrhosis (PBC). During the last decade, the mitochondrial autoantigens have been cloned, sequ enced, and identified as members of the 2-oxo-acid dehydrogenase pathw ay, including the E2 subunits of pyruvate dehydrogenase (PDC-E2), bran ched-chain 2-oxo-acid dehydrogenase (BCOADC-E2), and 2-oxo-glutarate d ehydrogenase (OGDC-E2). We have developed a rapid and sensitive diagno stic test for use in PBC based on a triple hybrid recombinant molecule (r-MIT3) that contains the autoepitopes of PDC-E2, BCOADC-E2, and OGD C-E2. To help understand the frequency and antigen specificity of AMAs in an asymptomatic population and to identify patients with early dis ease, we investigated the prevalence of AMA, by enzyme-linked immunoso rbent assay (ELISA), in a cohort of 1,530 people from northern Italy. Positive sera were further analyzed for immunoglobulin (Ig) isotypes, subclasses, and epitopes of AMA by a combination of ELISA and immunobl otting. In this cohort of 1,530 people, 9 (0.5%) reacted to r-MIT3 by ELISA. Of the 9 reactive sera, 2 recognized PDC-E2, 2 of 9 recognized BCOADC-E2, 1 of 9 recognized OGDC-E2, 2 of 9 recognized both PDC-E2 an d BCOADC-E2, and 1 of 9 recognized PDC-E2 and OGDC-E2. AMA reactivity was primarily IgM and IgA. Epitope mapping revealed an AMA pattern of reactivity to PDC-E2 that differed from that found in patients with hi stologically proven PBC in most of the sera. However, 1 sera of a 72-y ear-old female with a normal alkaline phosphatase had an AMA profile i dentical to typical PBC. After a variable follow-up period (8-14 month s), sera from 8 of 9 of these people were re-obtained for AMA and rela tive epitope mapping. Interestingly, the reactivity had a wider AMA pa ttern than before.