{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T16:52:20Z","timestamp":1765039940954,"version":"3.30.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5906,"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":[[1999,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Autoantibodies to the pyruvate dehydrogenase complex (PDC) are present in the serum of more than 95% of patients with primary biliary cirrhosis (PBC), the major epitope being the inner lipoyl domain of the E2 component. Immunoblotting suggests a similar prevalence of antibodies to a tightly associated lipoic acid-containing protein, E3 binding protein (;E3BP). Attempts to resolve E3BP from E2 have been unsuccessful, restricting study of the nature and significance of antibody responses to the individual proteins. In particular, it is unclear (;1) whether there is true cross-reactivity between E3BP and E2 and, if so, which is the originating response and (;2) whether autoantibodies preferentially bind a lipoylated epitope on E3BP as is the case with PDC-E2. In this study, complementary DNAs encoding rE2, full-length rE3BP, its single lipoyl domain (;rLip), and core domain (;rE3BPCore) were cloned, and the proteins were expressed in <jats:italic toggle=\"yes\">Escherichia coli.<\/jats:italic> Sera from 47 PBC patients were studied by immunoblotting and enzyme-linked immunosorbent assay (;ELISA) against rE2, rE3BP, rE3BPCore, and both unlipoylated (;U) and lipoylated (;L) rLip. All sera were reactive by ELISA to some degree with all recombinant proteins except rE3BPCore, to which only 6 of 47 showed any reactivity. Significant correlations (;<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .0001) were observed when comparing absorbance values for rE3BP with both rLip (;U) (;<jats:italic toggle=\"yes\">r<\/jats:italic> = 0.793) and (;L) (;<jats:italic toggle=\"yes\">r<\/jats:italic> = 0.963). The mean absorbance for rLip (;U, 0.26 \u00b1 0.05) was, however, significantly lower than the absorbance for rLip (;L) (;0.78 \u00b1 0.12; <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .0001). After probing by immunoblotting and elution of antibodies from rE2 and rE3BP, subsequent reprobing against the components in whole PDC revealed true cross-reactivity. In summary, the response to E3BP is primarily directed against the lipoylated domain of the protein. It still remains unclear, however, whether the initial breakdown of tolerance is to E2 or E3BP.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510300106","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:26:03Z","timestamp":1090999563000},"page":"21-26","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["Characterization of the autoantibody responses to recombinant E3 binding protein (protein X) of pyruvate dehydrogenase in primary biliary cirrhosis"],"prefix":"10.1097","volume":"30","author":[{"given":"Jeremy M.","family":"Palmer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David 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