{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:09:26Z","timestamp":1773306566734,"version":"3.50.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5997,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,4]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitochondrial antibodies (AMA) directed primarily against the E2 subunits of the pyruvate dehydrogenase complex, the branched chain 2\u2013oxo\u2013acid dehydrogenase complex, the 2\u2013oxoglutarate dehydrogenase complex, as well as the dihydrolipoamide dehydrogenase\u2013binding protein (E3BP) of pyruvate dehydrogenase complex. The autoantibody response to each E2 subunit is directed to the lipoic acid binding domain. However, hitherto, the epitope recognized by autoantibodies to E3BP has not been mapped. In this study, we have taken advantage of the recently available full\u2013length human E3BP complementary DNA (cDNA) to map this epitope. In addition, another lipoic binding protein, the H\u2013protein of the glycine cleavage complex, was also studied as a potential autoantigen recognized by AMA. Firstly, the sequence corresponding to the lipoic domain of E3BP (E3BP\u2013LD) was amplified by polymerase chain reaction and recombinant protein and then purified. Immunoreactivity of 45 PBC sera (and 52 control sera) against the purified recombinant E3BP\u2013LD was analyzed by enzyme\u2013linked immunosorbent assay (ELISA) and immunoblotting. Secondly, reactivity of PBC sera was similarly analyzed by immunoblotting against H\u2013protein. It is interesting that preabsorption of patient sera with the lipoic acid binding domain of E3BP completely removed all reactivity with the entire protein by immunoblotting analysis, suggesting that autoantibodies to E3BP are directed solely to its lipoic acid binding domain. Fifty\u2013three percent of PBC sera reacted with E3BP\u2013LD, with the majority of the response being of the immunoglobulin G (IgG) isotype (95%). Surprisingly, there was little IgM response to the E3BP\u2013LD suggesting that the immune response was secondary because of determinant spreading. In contrast, H\u2013protein does not appear to possess (or expose) autoepitopes recognized by PBC sera. This observation is consistent with structural data on this moiety.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510290403","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:45:08Z","timestamp":1091000708000},"page":"1013-1018","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":65,"title":["Autoepitope Mapping and Reactivity of Autoantibodies to the Dihydrolipoamide Dehydrogenase\u2013Binding Protein (E3bp) and the Glycine Cleavage Proteins in Primary Biliary Cirrhosis"],"prefix":"10.1097","volume":"29","author":[{"given":"Laurence","family":"Dubel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick 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