Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis

Standard

Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis. / Taubert, Richard; Engel, Bastian; Diestelhorst, Jana; Hupa-Breier, Katharina Luise; 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 Ph; 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; UK-AIH Consortium.

in: HEPATOLOGY, Jahrgang 75, Nr. 1, 01.2022, S. 13-27.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Taubert, R, Engel, B, Diestelhorst, J, Hupa-Breier, KL, Behrendt, P, Baerlecken, NT, Sühs, K-W, Janik, MK, Zachou, K, Sebode, M, Schramm, C, Londoño, M-C, Habes, S, Oo, YH, Lalanne, C, Pape, S, Schubert, M, Hust, M, Dübel, S, Thevis, M, Jonigk, D, Beimdiek, J, Buettner, FFR, Drenth, JP, Muratori, L, Adams, DH, Dyson, JK, Renand, A, Graupera, I, Lohse, AW, Dalekos, GN, Milkiewicz, P, Stangel, M, Maasoumy, B, Witte, T, Wedemeyer, H, Manns, MP, Jaeckel, E & UK-AIH Consortium 2022, 'Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis', HEPATOLOGY, Jg. 75, Nr. 1, S. 13-27. https://doi.org/10.1002/hep.32134

APA

Taubert, R., Engel, B., Diestelhorst, J., Hupa-Breier, K. L., Behrendt, P., Baerlecken, N. T., Sühs, K-W., Janik, M. K., Zachou, K., Sebode, M., Schramm, C., Londoño, M-C., Habes, S., Oo, Y. H., Lalanne, C., Pape, S., Schubert, M., Hust, M., Dübel, S., ... UK-AIH Consortium (2022). Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis. HEPATOLOGY, 75(1), 13-27. https://doi.org/10.1002/hep.32134

Vancouver

Taubert R, Engel B, Diestelhorst J, Hupa-Breier KL, Behrendt P, Baerlecken NT et al. Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis. HEPATOLOGY. 2022 Jan;75(1):13-27. https://doi.org/10.1002/hep.32134

Bibtex

@article{1e09c46157cd4e868b481afa3e1c2371,
title = "Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis",
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.",
author = "Richard Taubert and Bastian Engel and Jana Diestelhorst and Hupa-Breier, {Katharina Luise} and Patrick Behrendt and Baerlecken, {Niklas T} and Kurt-Wolfram S{\"u}hs and Janik, {Maciej K} and Kalliopi Zachou and Marcial Sebode and Christoph Schramm and Mar{\'i}a-Carlota Londo{\~n}o and Sarah Habes and Oo, {Ye H} and Claudine Lalanne and Simon Pape and Maren Schubert and Michael Hust and Stefan D{\"u}bel and Mario Thevis and Danny Jonigk and Julia Beimdiek and Buettner, {Falk F R} and Drenth, {Joost Ph} and Luigi Muratori and Adams, {David H} and Dyson, {Jessica K} and Am{\'e}d{\'e}e Renand and Isabel Graupera and Lohse, {Ansgar W} and Dalekos, {George N} and Piotr Milkiewicz and Martin Stangel and Benjamin Maasoumy and Torsten Witte and Heiner Wedemeyer and Manns, {Michael P} and Elmar Jaeckel and {UK-AIH Consortium}",
note = "This article is protected by copyright. All rights reserved.",
year = "2022",
month = jan,
doi = "10.1002/hep.32134",
language = "English",
volume = "75",
pages = "13--27",
journal = "HEPATOLOGY",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis

AU - Taubert, Richard

AU - Engel, Bastian

AU - Diestelhorst, Jana

AU - Hupa-Breier, Katharina Luise

AU - Behrendt, Patrick

AU - Baerlecken, Niklas T

AU - Sühs, Kurt-Wolfram

AU - Janik, Maciej K

AU - Zachou, Kalliopi

AU - Sebode, Marcial

AU - Schramm, Christoph

AU - Londoño, María-Carlota

AU - Habes, Sarah

AU - Oo, Ye H

AU - Lalanne, Claudine

AU - Pape, Simon

AU - Schubert, Maren

AU - Hust, Michael

AU - Dübel, Stefan

AU - Thevis, Mario

AU - Jonigk, Danny

AU - Beimdiek, Julia

AU - Buettner, Falk F R

AU - Drenth, Joost Ph

AU - Muratori, Luigi

AU - Adams, David H

AU - Dyson, Jessica K

AU - Renand, Amédée

AU - Graupera, Isabel

AU - Lohse, Ansgar W

AU - Dalekos, George N

AU - Milkiewicz, Piotr

AU - Stangel, Martin

AU - Maasoumy, Benjamin

AU - Witte, Torsten

AU - Wedemeyer, Heiner

AU - Manns, Michael P

AU - Jaeckel, Elmar

AU - UK-AIH Consortium

N1 - This article is protected by copyright. All rights reserved.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

U2 - 10.1002/hep.32134

DO - 10.1002/hep.32134

M3 - SCORING: Journal article

C2 - 34473365

VL - 75

SP - 13

EP - 27

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 1

ER -