{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:35:53Z","timestamp":1760297753101,"version":"3.30.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":8309,"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":[[1992,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Antimitochondrial autoantibodies are present in sera from close to 95% of patients with primary biliary cirrhosis. The so\u2013called primary biliary cirrhosis\u2013specific antigen, named M2, was found to be associated with an enzyme complex of the inner mitochondrial membrane and, more precisely, with the E2 component, dihydrolipoamide acetyltransferase, of the pyruvate dehydrogenase complex. We recently established that an immunodominant epitope recognized in direct enzyme\u2013linked immunosorbent assay by primary biliary cirrhosis M2<jats:sup>+<\/jats:sup> sera, but not by non\u2014primary biliary cirrhosis M2<jats:sup>+<\/jats:sup> sera, could be mimicked by a synthetic peptide encompassing residues 167-184 of the E2 component and associated with lipoic acid. This fragment is present in the natural inner lipoyl\u2013binding site of the human enzyme, and the presence of lipoic acid located on Iysine 173 was found to be essential to allow IgG antibody binding. In this study we have improved the enzyme\u2013linked immunosorbent assay test based on the synthetic peptide\u2014lipoic acid conjugate by using a multiple antigen peptide system containing eight copies of the peptide as antigen. This approach avoids the use of a peptide conjugated to a carrier protein and was found to be particularly efficient because 23 of 27 primary biliary cirrhosis M2<jats:sup>+<\/jats:sup> sera (85%) could be identified. A multiple antigen peptide without lipoic acid was not recognized by primary biliary cirrhosis antibodies. The peptide used in the multiple antigen peptide construction was a short 13\u2013mer peptide encompassing a highly conserved sequence present in both the outer (residues 40-52) and the inner (residues 167-179) lipoyl\u2013binding sites of the enzyme. Our results thus confirm that the highly conserved lipoate site, when associated with lipoic acid, constitutes a major conformational epitope of E2. The multiple antigen peptide construction with peptide\u2014lipoic acid conjugate could be used as a valuable probe for primary biliary cirrhosis diagnosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840160615","type":"journal-article","created":{"date-parts":[[2007,3,4]],"date-time":"2007-03-04T01:21:08Z","timestamp":1172971268000},"page":"1395-1403","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["Multiple Autoepitope Presentation for Specific Detection of Antibodies in Primary Biliary Cirrhosis"],"prefix":"10.1097","volume":"16","author":[{"given":"Jean-Paul","family":"Briand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Andre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Tuaillon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Herve","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Neimark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylviane","family":"Muller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840160615-BIB1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1159\/000235131","volume":"91","author":"Tuaillon","year":"1990","journal-title":"Int Arch Allergy Appl Immunol"},{"key":"10.1002\/hep.1840160615-BIB2","doi-asserted-by":"crossref","first-page":"8176","DOI":"10.1073\/pnas.85.21.8176","volume":"85","author":"Muller","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840160615-BIB3","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1084\/jem.169.5.1607","volume":"169","author":"Plau\u00e9","year":"1989","journal-title":"J Exp Med"},{"key":"10.1002\/hep.1840160615-BIB4","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/art.1780340509","volume":"34","author":"Hines","year":"1991","journal-title":"Arthritis Rheum"},{"key":"10.1002\/hep.1840160615-BIB5","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1365-2249.1990.tb03327.x","volume":"81","author":"Barakat","year":"1990","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840160615-BIB6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1365-2249.1991.tb05776.x","volume":"86","author":"Barakat","year":"1991","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840160615-BIB7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.1365-2249.1992.tb06874.x","volume":"89","author":"Barakat","year":"1992","journal-title":"Clin Exp Immunol"},{"key":"10.1002\/hep.1840160615-BIB8","doi-asserted-by":"crossref","first-page":"7419","DOI":"10.1073\/pnas.83.19.7419","volume":"83","author":"Elkon","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840160615-BIB9","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1172\/JCI113607","volume":"82","author":"Lieu","year":"1988","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840160615-BIB10","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4049\/jimmunol.148.2.445","volume":"148","author":"Tuaillon","year":"1992","journal-title":"J Immunol"},{"key":"10.1002\/hep.1840160615-BIB11","first-page":"123","volume-title":"Autoimmune liver diseases","author":"Berg","year":"1991","unstructured":". Autoantibody patterns in primary biliary cirrhosis. In: , eds. Autoimmune liver diseases. New York: Raven Press, 1991: 123\u2013142."},{"key":"10.1002\/hep.1840160615-BIB12","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/0016-5085(91)80033-6","volume":"100","author":"Gershwin","year":"1991","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840160615-BIB13","doi-asserted-by":"crossref","first-page":"8971","DOI":"10.1016\/S0021-9258(19)38795-2","volume":"265","author":"Reed","year":"1990","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840160615-BIB14","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.4049\/jimmunol.138.10.3525","volume":"138","author":"Gershwin","year":"1987","journal-title":"J Immunol"},{"key":"10.1002\/hep.1840160615-BIB15","doi-asserted-by":"crossref","first-page":"7317","DOI":"10.1073\/pnas.85.19.7317","volume":"85","author":"Coppel","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840160615-BIB16","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/978-94-011-3034-9_84","volume-title":"Peptides 1990: proceedings of the twenty first European peptide symposium","author":"Neimark","year":"1991","unstructured":". An automated device for solid-phase multiple peptide synthesis. In: , eds. Peptides 1990: proceedings of the twenty first European peptide symposium. 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Application and limitations of the multiple antigen peptide (MAP) system in the production and evaluation of anti-peptide and anti-protein antibodies. J Immunol Methods 1992 (in press)."},{"key":"10.1002\/hep.1840160615-BIB30","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1084\/jem.167.6.1791","volume":"167","author":"Van De Water","year":"1988","journal-title":"J Exp Med"},{"key":"10.1002\/hep.1840160615-BIB31","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.4049\/jimmunol.144.9.3367","volume":"144","author":"Surh","year":"1990","journal-title":"J Immunol"},{"key":"10.1002\/hep.1840160615-BIB32","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.4049\/jimmunol.144.7.2647","volume":"144","author":"Surh","year":"1990","journal-title":"J Immunol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.1840160615","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-199212000-00014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:07:10Z","timestamp":1733051230000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-199212000-00014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,12]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1992]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.1840160615","relation":{},"ISSN":["0270-9139"],"issn-type":[{"type":"print","value":"0270-9139"}],"subject":[],"published":{"date-parts":[[1992,12]]}}}