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Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis.
Taubert, Richard; Engel, Bastian; Diestelhorst, Jana; Hupa-Breier, Katharina L; Behrendt, Patrick; Baerlecken, Niklas T; Sühs, Kurt-Wolfram; Janik, Maciej K; Zachou, Kalliopi; Sebode, Marcial; Schramm, Christoph; Londoño, María-Carlota; Habes, Sarah; Oo, Ye H; Lalanne, Claudine; Pape, Simon; Schubert, Maren; Hust, Michael; Dübel, Stefan; Thevis, Mario; Jonigk, Danny; Beimdiek, Julia; Buettner, Falk F R; Drenth, Joost P H; Muratori, Luigi; Adams, David H; Dyson, Jessica K; Renand, Amédée; Graupera, Isabel; Lohse, Ansgar W; Dalekos, George N; Milkiewicz, Piotr; Stangel, Martin; Maasoumy, Benjamin; Witte, Torsten; Wedemeyer, Heiner; Manns, Michael P; Jaeckel, Elmar.
Afiliação
  • Taubert R; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • Engel B; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Diestelhorst J; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • Hupa-Breier KL; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Behrendt P; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • Baerlecken NT; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Sühs KW; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • Janik MK; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Zachou K; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  • Sebode M; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Schramm C; 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.
  • Londoño MC; German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
  • Habes S; Department of Clinical Immunology, Hannover Medical School, Hannover, Germany.
  • Oo YH; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Lalanne C; Liver and Internal Medicine Unit, Medical University of Warsaw, Warsaw, Poland.
  • Pape S; Institute of Internal Medicine and Hepatology, Larissa, Greece.
  • Schubert M; 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.
  • Hust M; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Dübel S; 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • Thevis M; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Jonigk D; 1st Department of Medicine, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • Beimdiek J; Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • Buettner FFR; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Drenth JPH; Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain.
  • Muratori L; Hépato-Gastro-entérologie et Assistance Nutritionnelle, CHU Nantes, Nantes, France.
  • Dyson JK; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Renand A; Centre for Liver and Gastro Research, Institute of Immunology and Immunotherapy, The Medical School, National Institute of Health Research Birmingham Biomedical Research Centre, Birmingham, UK.
  • Graupera I; Liver Transplant and Hepatobiliary Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.
  • Lohse AW; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
  • Dalekos GN; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
  • Milkiewicz P; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Stangel M; Institute for Biochemistry, Biotechnology and Bioinformatics, Department of Biotechnology, Technische Universität Braunschweig, Braunschweig, Germany.
  • Maasoumy B; Institute for Biochemistry, Biotechnology and Bioinformatics, Department of Biotechnology, Technische Universität Braunschweig, Braunschweig, Germany.
  • Witte T; Institute for Biochemistry, Biotechnology and Bioinformatics, Department of Biotechnology, Technische Universität Braunschweig, Braunschweig, Germany.
  • Wedemeyer H; Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.
  • Manns MP; Institute for Pathology, Hannover Medical School, Hannover, Germany.
  • Jaeckel E; Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
Hepatology ; 75(1): 13-27, 2022 01.
Article em En | MEDLINE | ID: mdl-34473365
ABSTRACT
BACKGROUND AND

AIMS:

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. APPROACH AND

RESULTS:

During the search for more-precise autoantibodies to distinguish AIH from non-AIH liver diseases (non-AIH-LD), IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macroarray and confirmed with solid-phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) was exemplarily quantified by reactivity against human huntingtin-interacting protein 1-related 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%-20% 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-AIH-LD.

CONCLUSIONS:

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-negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autoanticorpos / Imunoglobulina G / Hepatite Autoimune Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autoanticorpos / Imunoglobulina G / Hepatite Autoimune Tipo de estudo: Diagnostic_studies / Observational_studies / Prognostic_studies Limite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2022 Tipo de documento: Article