{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:46:16Z","timestamp":1790505976985,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for the workup of AIH lack either sensitivity or specificity, leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macroarray.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>During the search for more\u2010precise autoantibodies to distinguish AIH from non\u2010AIH liver diseases (non\u2010AIH\u2010LD), IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macroarray and confirmed with solid\u2010phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) was exemplarily quantified by reactivity against human huntingtin\u2010interacting protein 1\u2010related protein in bovine serum albumin blocked ELISA (HIP1R\/BSA). The diagnostic fidelity of HIP1R\/BSA binding pIgG to diagnose AIH was assessed in a retrospective training, a retrospective multicenter validation, and a prospective validation cohort in cryoconserved samples from 1,568 adults from 10 centers from eight countries. Reactivity against HIP1R\/BSA had a 25% and 14% higher specificity to diagnose AIH than conventional antinuclear and antismooth muscle antibodies, a significantly higher sensitivity than liver kidney microsomal antibodies and antisoluble liver antigen\/liver pancreas antigen, and a 12%\u201320% higher accuracy than conventional autoantibodies. Importantly, HIP1R\/BSA reactivity was present in up to 88% of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy, pIgG returns to background levels of non\u2010AIH\u2010LD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>pIgG could be used as a promising marker to improve the diagnostic workup of liver diseases with a higher specificity for AIH compared to conventional autoantibodies and a utility in autoantibody\u2010negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32134","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T10:56:06Z","timestamp":1630580166000},"page":"13-27","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":46,"title":["Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis"],"prefix":"10.1097","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-2496","authenticated-orcid":false,"given":"Richard","family":"Taubert","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-3454","authenticated-orcid":false,"given":"Bastian","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Diestelhorst","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina L.","family":"Hupa\u2010Breier","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Behrendt","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology,Hannover Medical School,Hannover,Germany"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"},{"name":"TWINCORE,Centre for Experimental and Clinical Infection Research,a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI),Hannover,Germany"},{"name":"German Center for Infectious Disease Research (DZIF),Partner Site Hannover\u2010Braunschweig,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas T.","family":"Baerlecken","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology,Hannover Medical School,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt\u2010Wolfram","family":"S\u00fchs","sequence":"additional","affiliation":[{"name":"Department of Neurology,Hannover Medical School,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej K.","family":"Janik","sequence":"additional","affiliation":[{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"},{"name":"Liver and Internal Medicine Unit,Medical University of Warsaw,Warsaw,Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Zachou","sequence":"additional","affiliation":[{"name":"Institute of Internal Medicine and Hepatology,Larissa,Greece"},{"name":"Department of Medicine and Research Laboratory of Internal Medicine,National Expertise Center of Greece in Autoimmune Liver Diseases,General University Hospital of Larissa,Larissa,Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5163-6979","authenticated-orcid":false,"given":"Marcial","family":"Sebode","sequence":"additional","affiliation":[{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"},{"name":"1st Department of Medicine,University Medical Centre Hamburg\u2010Eppendorf (UKE),Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schramm","sequence":"additional","affiliation":[{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"},{"name":"1st Department of Medicine,University Medical Centre Hamburg\u2010Eppendorf (UKE),Hamburg,Germany"},{"name":"Martin Zeitz Centre for Rare Diseases,University Medical Centre Hamburg\u2010Eppendorf (UKE),Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-1586","authenticated-orcid":false,"given":"Mar\u00eda\u2010Carlota","family":"Londo\u00f1o","sequence":"additional","affiliation":[{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"},{"name":"Liver Unit,Hospital Cl\u00ednic Barcelona,IDIBAPS,CIBEREHD,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Habes","sequence":"additional","affiliation":[{"name":"H\u00e9pato\u2010Gastro\u2010ent\u00e9rologie et Assistance Nutritionnelle,CHU Nantes,Nantes,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the UK\u2010AIH Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye H.","family":"Oo","sequence":"additional","affiliation":[{"name":"European Reference Network on Hepatological Diseases (ERN 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Schubert","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry, Biotechnology and Bioinformatics,Department of Biotechnology,Technische Universit\u00e4t Braunschweig,Braunschweig,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hust","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry, Biotechnology and Bioinformatics,Department of Biotechnology,Technische Universit\u00e4t Braunschweig,Braunschweig,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"D\u00fcbel","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry, Biotechnology and Bioinformatics,Department of Biotechnology,Technische Universit\u00e4t 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H.","family":"Drenth","sequence":"additional","affiliation":[{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"},{"name":"Department of Gastroenterology and Hepatology,Radboud University Medical Center,Nijmegen,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Muratori","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences,University of Bologna,Bologna,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-0336","authenticated-orcid":false,"given":"David H.","family":"Adams","sequence":"additional","affiliation":[{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER),Hamburg,Germany"},{"name":"Centre for Liver and Gastro Research,Institute of Immunology and Immunotherapy,The Medical School,National Institute of Health Research Birmingham Biomedical Research 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