{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:47:36Z","timestamp":1789001256541,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T00:00:00Z","timestamp":1412899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006370","name":"SBIR","doi-asserted-by":"crossref","award":["R44 AI052525"],"award-info":[{"award-number":["R44 AI052525"]}],"id":[{"id":"10.13039\/100006370","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,2]]},"abstract":"Abstract<\/jats:title>Background & Aims<\/jats:title>Using high\u2010density human recombinant protein microarrays, we identified two potential biomarkers, kelch\u2010like 12 (KLHL<\/jats:styled-content>12) and hexokinase\u20101 (HK<\/jats:styled-content>1), in primary biliary cirrhosis (PBC<\/jats:styled-content>). The objective of this study was to determine the diagnostic value of anti\u2010KLHL<\/jats:styled-content>12\/HK<\/jats:styled-content>1 autoantibodies in PBC<\/jats:styled-content>. Initial discovery used sera from 22 patients with PBC<\/jats:styled-content> and 62 non\u2010PBC<\/jats:styled-content> controls. KLHL<\/jats:styled-content>12 and HK<\/jats:styled-content>1 proteins were then analysed for immunoglobulin reactivity by immunoblot and enzyme\u2010linked immunosorbent assay (ELISA<\/jats:styled-content>) in two independent cohorts of PBC<\/jats:styled-content> and disease\/healthy control patients.<\/jats:p><\/jats:sec>Methods<\/jats:title>Serum samples from 100 patients with PBC<\/jats:styled-content> and 165 non\u2010PBC<\/jats:styled-content> disease controls were analysed by immunoblot and samples from 366 patients with PBC<\/jats:styled-content>, 174 disease controls, and 80 healthy donors were tested by ELISA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Results<\/jats:title>Anti\u2010KLHL<\/jats:styled-content>12 and anti\u2010HK<\/jats:styled-content>1 antibodies were each detected more frequently in PBC<\/jats:styled-content> compared with non\u2010PBC<\/jats:styled-content> disease controls (P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.001). Not only are both markers highly specific for PBC<\/jats:styled-content> (\u226595%) but they also yielded higher sensitivity than anti\u2010gp210 and anti\u2010sp100 antibodies. Combining anti\u2010HK<\/jats:styled-content>1 and anti\u2010KLHL<\/jats:styled-content>12 with available markers (MIT<\/jats:styled-content>3, gp210 and sp100), increased the diagnostic sensitivity for PBC<\/jats:styled-content>. Most importantly, anti\u2010KLHL<\/jats:styled-content>12 and anti\u2010HK<\/jats:styled-content>1 antibodies were present in 10\u201335% of anti\u2010mitochondrial antibody (AMA<\/jats:styled-content>)\u2010negative PBC<\/jats:styled-content> patients and adding these two biomarkers to conventional PBC<\/jats:styled-content> assays dramatically improved the serological sensitivity in AMA<\/jats:styled-content>\u2010negative PBC<\/jats:styled-content> from 55% to 75% in immunoblot and 48.3% to 68.5% in ELISA<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The addition of tests for highly specific anti\u2010KLHL<\/jats:styled-content>12 and anti\u2010HK<\/jats:styled-content>1 antibodies to AMA<\/jats:styled-content> and ANA<\/jats:styled-content> serological assays significantly improves efficacy in the clinical detection and diagnosis of PBC<\/jats:styled-content>, especially for AMA<\/jats:styled-content>\u2010negative subjects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12690","type":"journal-article","created":{"date-parts":[[2014,9,19]],"date-time":"2014-09-19T14:05:27Z","timestamp":1411135527000},"page":"642-651","source":"Crossref","is-referenced-by-count":82,"title":["Anti\u2010kelch\u2010like 12 and anti\u2010hexokinase 1: novel autoantibodies in primary biliary cirrhosis"],"prefix":"10.1111","volume":"35","author":[{"given":"Gary L.","family":"Norman","sequence":"first","affiliation":[{"name":"Inova Diagnostics San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Yen","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology University of California Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather P.","family":"Ostendorff","sequence":"additional","affiliation":[{"name":"AmberGen, Inc. 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Watertown MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon M.","family":"Hirschfield","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research Centre for Liver Research University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Liver and Internal Medicine Unit Department of General, Transplant and Liver Surgery Medical University of Warsaw Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald B.","family":"Bloch","sequence":"additional","affiliation":[{"name":"The Center for Immunology and Inflammatory Diseases and the Division of Rheumatology Allergy and Immunology of the General Medical Services and the Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School Harvard MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Rothschild","sequence":"additional","affiliation":[{"name":"AmberGen, Inc. 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