Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis
Richard Taubert
(1, 2)
,
Bastian Engel
(1, 2)
,
Jana Diestelhorst
(1, 2)
,
Katharina Hupa-Breier
(1, 2)
,
Patrick Behrendt
(1, 2, 3, 4)
,
Niklas Baerlecken
(1)
,
Kurt‐wolfram Sühs
(1)
,
Maciej Janik
(2, 5)
,
Kalliopi Zachou
(6)
,
Marcial Sebode
(2, 7)
,
Christoph Schramm
(7, 2)
,
María‐carlota Londoño
(2, 8, 9, 10)
,
Sarah Habes
(11)
,
Ye Oo
(2, 12, 13)
,
Claudine Lalanne
(14)
,
Simon Pape
(2, 15)
,
Maren Schubert
(16)
,
Michael Hust
(16)
,
Stefan Dübel
(16)
,
Mario Thevis
(17)
,
Danny Jonigk
(1)
,
Julia Beimdiek
(1)
,
Falk Buettner
(1)
,
Joost Drenth
(2, 15)
,
Luigi Muratori
(14)
,
David Adams
(2, 12, 13)
,
Jessica Dyson
(18, 19)
,
Amédée Renand
(20, 21)
,
Isabel Graupera
(2, 8, 9, 10)
,
Ansgar Lohse
(2, 7)
,
George Dalekos
(6)
,
Piotr Milkiewicz
(2, 5, 22)
,
Martin Stangel
(1)
,
Benjamin Maasoumy
(2, 1)
,
Torsten Witte
(1)
,
Heiner Wedemeyer
(2, 1)
,
Michael Manns
(2, 1)
,
Elmar Jaeckel
(2, 1, 23)
1
MHH -
Medizinische Hochschule Hannover = Hannover Medical School
2 ERN - RARE - LIVER - European Reference Network on Hepatological Diseases [Hamburg, Germany]
3 TWINCORE - Centre for Experimental and Clinical Infection Research [Hanover]
4 HZI - Helmholtz Centre for Infection Research
5 Medical University of Warsaw - Poland
6 University Hospital of Larissa
7 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
8 Clinic Barcelona Hospital Universitari
9 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
10 CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
11 Service d'hépato-gastroentérologie [CHU Nantes]
12 NIHR Biomedical Research Centre [London]
13 Birmingham Women's and Children's NHS Foundation Trust
14 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
15 RadboudUMC - Radboud University Medical Center [Nijmegen]
16 Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig]
17 German Sport University Cologne [Germany]
18 Newcastle Upon Tyne Hospitals NHS Foundation Trust
19 Newcastle University [Newcastle]
20 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
21 Team 4 - U1064 Inserm - CR2TI - Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t)
22 PUM - Pomeranian Medical University [Szczecin]
23 University of Toronto
2 ERN - RARE - LIVER - European Reference Network on Hepatological Diseases [Hamburg, Germany]
3 TWINCORE - Centre for Experimental and Clinical Infection Research [Hanover]
4 HZI - Helmholtz Centre for Infection Research
5 Medical University of Warsaw - Poland
6 University Hospital of Larissa
7 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
8 Clinic Barcelona Hospital Universitari
9 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
10 CIBERehd - Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas
11 Service d'hépato-gastroentérologie [CHU Nantes]
12 NIHR Biomedical Research Centre [London]
13 Birmingham Women's and Children's NHS Foundation Trust
14 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
15 RadboudUMC - Radboud University Medical Center [Nijmegen]
16 Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig]
17 German Sport University Cologne [Germany]
18 Newcastle Upon Tyne Hospitals NHS Foundation Trust
19 Newcastle University [Newcastle]
20 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
21 Team 4 - U1064 Inserm - CR2TI - Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t)
22 PUM - Pomeranian Medical University [Szczecin]
23 University of Toronto
Richard Taubert
- Fonction : Auteur
- PersonId : 1300512
- ORCID : 0000-0001-9270-2496
Bastian Engel
- Fonction : Auteur
- PersonId : 1300513
- ORCID : 0000-0002-0972-3454
María‐carlota Londoño
- Fonction : Auteur
- PersonId : 1300515
- ORCID : 0000-0002-6533-1586
David Adams
- Fonction : Auteur
- PersonId : 1300516
- ORCID : 0000-0001-6776-0336
Isabel Graupera
- Fonction : Auteur
Résumé
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.
Domaines
Sciences du Vivant [q-bio]Origine | Publication financée par une institution |
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