{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:09:34Z","timestamp":1789650574191,"version":"4.0.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3106,"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":[[2007,3]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      <jats:bold>The antimitochondrial response in primary biliary cirrhosis (PBC) is the most highly directed and specific self-reacting antibody in human immunopathology. Originally, antimitochondrial antibodies (AMAs) were detected by indirect immunofluorescence (IIF) and found in approximately 90% of well-documented patients with PBC. The introduction of recombinant autoantigens and the use of immunoblotting have increased the sensitivity and specificity of AMAs, and they are now considered positive in approximately 95% of patients with PBC. Clearly, accurate autoantibody detection represents one of the fundamental requirements for reliable diagnostics in autoimmunity. To address the 5% of AMA-negative patients with PBC, we have generated and validated a bead assay for the detection of AMA. We enrolled 120 patients with PBC, including a non-random group of 30 rigorously proven AMA-negative patients, 50 healthy subjects, and 74 controls with autoimmune diseases (18 with primary sclerosing cholangitis, 16 with autoimmune hepatitis, and 40 with systemic lupus erythematosus). Individual bead assays were done with the three mitochondrial autoantigens, PDC-E2, BCOADC-E2, and OGDC-E2. As expected, 90 of 90 previously known AMA-positive patients remained positive with this assay but, interestingly, 20% of the rigorously defined AMA-negative patient group had antibodies to one or more of the mitochondrial autoantigens. Furthermore, 100% of these newly detected AMA-positive patients were anti-nuclear antibody (ANA) positive.<\/jats:bold>\n                      <jats:bold>Conclusion:<\/jats:bold>\n                      <jats:bold>The development of this assay reflects the potential for automated detection with rapid and reliable assaying and further highlights the diminished number of truly AMA-negative PBC patients. (Hepatology 2007;45:659\u2013665.)<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.21583","type":"journal-article","created":{"date-parts":[[2007,2,26]],"date-time":"2007-02-26T17:09:40Z","timestamp":1172509780000},"page":"659-665","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":139,"title":["A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis"],"prefix":"10.1097","volume":"45","author":[{"given":"Sabine","family":"Oertelt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Rieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Selmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Invernizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aftab A.","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross L.","family":"Coppel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Podda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.C.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Gershwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-13-20241201","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S1542-3565(03)00134-4","article-title":"Natural history of pruritus in primary biliary cirrhosis.","volume":"1","author":"Talwalkar","year":"2003","journal-title":"Clin Gastroenterol Hepatol"},{"key":"R2-13-20241201","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1056\/NEJMra043898","article-title":"Primary biliary cirrhosis.","volume":"353","author":"Kaplan","year":"2005","journal-title":"N Engl J Med"},{"key":"R3-13-20241201","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1053\/jhep.2001.26514","article-title":"Detection of antimitochondrial autoantibodies in immunofluorescent AMAnegative patients with primary biliary cirrhosis using recombinant autoantigens.","volume":"34","author":"Miyakawa","year":"2001","journal-title":"Hepatology"},{"key":"R4-13-20241201","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/S1089-3261(03)00104-1","article-title":"Antimitochondrial and other autoantibodies.","volume":"7","author":"Bogdanos","year":"2003","journal-title":"Clin Liver Dis"},{"key":"R5-13-20241201","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0022-1759(00)00238-6","article-title":"Multiplexed particlebased flow cytometric assays.","volume":"243","author":"Vignali","year":"2000","journal-title":"J Immunol Methods"},{"key":"R6-13-20241201","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00432479","article-title":"Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis).","volume":"379","author":"Ludwig","year":"1978","journal-title":"Virchows Arch A Pathol Anat Histol"},{"key":"R7-13-20241201","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.4049\/jimmunol.138.10.3525","article-title":"Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis.","volume":"138","author":"Gershwin","year":"1987","journal-title":"J Immunol"},{"key":"R8-13-20241201","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1055\/s-2008-1040504","article-title":"Molecular definitions, autoepitopes, and enzymatic activities of the mitochondrial autoantigens of primary biliary cirrhosis.","volume":"9","author":"Van de Water","year":"1989","journal-title":"Semin Liver Dis"},{"key":"R9-13-20241201","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/hep.1840110502","article-title":"The relative affinity of recombinant dihydrolipoamide transacetylase for autoantibodies in primary biliary cirrhosis.","volume":"11","author":"Robertson","year":"1990","journal-title":"Hepatology"},{"key":"R10-13-20241201","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1084\/jem.167.6.1791","article-title":"The autoepitope of the 74kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase.","volume":"167","author":"Van de Water","year":"1988","journal-title":"J Exp Med"},{"key":"R11-13-20241201","doi-asserted-by":"crossref","first-page":"5157","DOI":"10.4049\/jimmunol.161.10.5157","article-title":"Monoclonal antibodies to mitochondrial E2 components define autoepitopes in primary biliary cirrhosis.","volume":"161","author":"Migliaccio","year":"1998","journal-title":"J Immunol"},{"key":"R12-13-20241201","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1055\/s-2005-916321","article-title":"Antinuclear antibodies in primary biliary cirrhosis.","volume":"25","author":"Invernizzi","year":"2005","journal-title":"Semin Liver Dis"},{"key":"R13-13-20241201","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.4049\/jimmunol.144.7.2647","article-title":"Comparative epitope mapping of murine monoclonal and human autoantibodies to human PDHE2, the major mitochondrial autoantigen of primary biliary cirrhosis.","volume":"144","author":"Surh","year":"1990","journal-title":"J Immunol"},{"key":"R14-13-20241201","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/hep.510270303","article-title":"Characterization of antimitochondrial antibodies in health adults.","volume":"27","author":"Mattalia","year":"1998","journal-title":"Hepatology"},{"key":"R15-13-20241201","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.4049\/jimmunol.152.5.2577","article-title":"Nucleotide sequence analysis of natural and combinatorial antiPDCE2 antibodies in patients with primary biliary cirrhosis: recapitulating immune selection with molecular biology.","volume":"152","author":"Pascual","year":"1994","journal-title":"J Immunol"},{"key":"R16-13-20241201","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1034\/j.1600-0528.2002.017402.x","article-title":"Primary biliary cirrhosis: an orchestrated immune response against epithelial cells.","volume":"174","author":"Gershwin","year":"2000","journal-title":"Immunol Rev"},{"key":"R17-13-20241201","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/hep.1840150302","article-title":"Use of designer recombinant mitochondrial antigens in the diagnosis of primary biliary cirrhosis.","volume":"15","author":"Leung","year":"1992","journal-title":"Hepatology"},{"key":"R18-13-20241201","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1056\/NEJM198905253202104","article-title":"Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis.","volume":"320","author":"Van de Water","year":"1989","journal-title":"N Engl J Med"},{"key":"R19-13-20241201","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/hep.510240117","article-title":"Use of a designer triple expression hybrid clone for three different lipoyl domain for the detection of antimitochondrial autoantibodies.","volume":"24","author":"Moteki","year":"1996","journal-title":"Hepatology"},{"key":"R20-13-20241201","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1600-0676.1997.tb01033.x","article-title":"Clinicopathological study of primary biliary cirrhosis negative for antimitochondrial antibodies.","volume":"17","author":"Nakanuma","year":"1997","journal-title":"Liver"},{"key":"R21-13-20241201","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1093\/clinchem\/43.9.1749","article-title":"Advanced multiplexed analysis with the FlowMetrix system.","volume":"43","author":"Fulton","year":"1997","journal-title":"Clin Chem"},{"key":"R22-13-20241201","first-page":"133","article-title":"Simultaneous detection of 15 human cytokines in a single sample of stimulated peripheral blood mononuclear cells.","volume":"10","author":"de Jager","year":"2003","journal-title":"Clin Diagn Lab Immunol"},{"key":"R23-13-20241201","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jim.2004.02.010","article-title":"A novel method of multiplexed competitive antibody binning for the characterization of monoclonal antibodies.","volume":"288","author":"Jia","year":"2004","journal-title":"J Immunol Methods"},{"key":"R24-13-20241201","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.4049\/jimmunol.144.9.3367","article-title":"Structural requirement for autoreactivity on human pyruvate dehydrogenaseE2, the major autoantigen of primary biliary cirrhosis: implication for a conformational autoepitope.","volume":"144","author":"Surh","year":"1990","journal-title":"J Immunol"},{"key":"R25-13-20241201","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1572-0241.2003.07270.x","article-title":"Positive markers in AMAnegative PBC.","volume":"98","author":"Vergani","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"R26-13-20241201","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/S0168-8278(00)00040-4","article-title":"Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis.","volume":"34","author":"Invernizzi","year":"2001","journal-title":"J Hepatol"},{"key":"R27-13-20241201","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1002\/hep.21172","article-title":"Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis.","volume":"43","author":"WesierskaGadek","year":"2006","journal-title":"Hepatology"},{"key":"R28-13-20241201","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1196\/annals.1361.043","article-title":"Clinical relevance of antiphospholipid antibodies in primary biliary cirrhosis.","volume":"1051","author":"von Landenberg","year":"2005","journal-title":"Ann N Y Acad Sci"},{"key":"R29-13-20241201","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1046\/j.1365-2249.1998.00735.x","article-title":"Antibody to carbonic anhydrase II is present in primary biliary cirrhosis (PBC) irrespective of antimitochondrial antibody status.","volume":"114","author":"Invernizzi","year":"1998","journal-title":"Clin Exp Immunol"},{"key":"R30-13-20241201","first-page":"113","article-title":"Antineutrophil nuclear antibodies (ANNA) in primary biliary cirrhosis: their prevalence and antigen specificity.","volume":"35","author":"Orth","year":"1997","journal-title":"Z Gastroenterol"},{"key":"R31-13-20241201","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S1568-9972(03)00013-2","article-title":"Antinuclear antibodies specific for primary biliary cirrhosis.","volume":"2","author":"Worman","year":"2003","journal-title":"Autoimmun Rev"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.21583","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200703000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T08:17:22Z","timestamp":1733041042000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200703000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.21583","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2007,3]]}}}