Detection of polyreactive immunoglobulin G facilitates diagnosis in children with autoimmune hepatitis.

Autor: Engel B; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany. Engel.Bastian@mh-hannover.de.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany. Engel.Bastian@mh-hannover.de., Diestelhorst J; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Nephrology, Hepatology and Metabolic Disorders, Hannover Medical School, Hannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Oncology, Hemostaseology and Palliative Care, Johannes Wesling Medical Center Minden, University Clinic for Haematology, UKRUB, University of Bochum, Minden, Germany., Hupa-Breier KL; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Kirchner T; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Henjes N; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Loges S; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Yuksel M; Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College Hospital, King's College London, London, UK.; Koç University Research Centre for Translational Medicine (KUTTAM)-Liver Immunology Lab, Istanbul, Turkey.; Department of Biomedical Sciences, College of Liberal Arts and Life Sciences, University of Westminster, London, UK., Janczyk W; Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Lalanne C; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Zachou K; Institute of Internal Medicine and Hepatology, Larissa, Greece.; l University Hospital of Larissa, Larissa, Greece.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Oo YH; Centre for Liver and Gastro Research, National Institute of Health Research Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, The Medical School, Birmingham, United Kingdom & Liver transplant and Hepatobiliary Unit, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Gournay J; Institut Des Maladies de L'Appareil Digestif (IMAD), Nantes Université, CHU Nantes, Hépato-Gastro-Entérologie, Inserm CIC 1413, 44000, Nantes, France., Pape S; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Drenth JPH; Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Renand A; Center for Research in Transplantation and Translational Immunology, Nantes Université, UMR 1064, Inserm, 44000, Nantes, France., Dalekos GN; Institute of Internal Medicine and Hepatology, Larissa, Greece.; l University Hospital of Larissa, Larissa, Greece.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Muratori L; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Socha P; Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Ma Y; Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College Hospital, King's College London, London, UK., Arikan C; Koç University Research Centre for Translational Medicine (KUTTAM)-Liver Immunology Lab, Istanbul, Turkey.; Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Koç University School of Medicine, Istanbul, 34010, Turkey., Baumann U; Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Nephrology, Hepatology and Metabolic Disorders, Hannover Medical School, Hannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Manns MP; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Wedemeyer H; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Junge N; Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Nephrology, Hepatology and Metabolic Disorders, Hannover Medical School, Hannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany., Jaeckel E; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.; Ajmera Transplant Center, Toronto General Hospital, United Health Network, University of Toronto, Toronto, Canada., Taubert R; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, HepatologyHannover, Germany.; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), Hamburg, Germany.
Jazyk: angličtina
Zdroj: Hepatology international [Hepatol Int] 2024 Aug; Vol. 18 (4), pp. 1214-1226. Date of Electronic Publication: 2024 Jul 08.
DOI: 10.1007/s12072-024-10695-1
Abstrakt: Objective: The detection of autoantibodies is essential to diagnose autoimmune hepatitis (AIH). Particularly in children, specificity of autoantibodies decreases due to lower titers being diagnostic and being present not only in AIH but also in other liver diseases. Recently, quantification of polyreactive IgG (pIgG) for detection of adult AIH showed the highest overall accuracy compared to antinuclear antibodies (ANA), anti-smooth muscle antibodies (anti-SMA), anti-liver kidney microsomal antibodies (anti-LKM) and anti-soluble liver antigen/liver pancreas antibodies (anti-SLA/LP). We aimed to evaluate the diagnostic value of pIgG for pediatric AIH.
Design: pIgG, quantified using HIP1R/BSA coated ELISA, and immunofluorescence on rodent tissue sections were performed centrally. The diagnostic fidelity to diagnose AIH was compared to conventional autoantibodies of AIH in training and validation cohorts from a retrospective, European multi-center cohort from nine centers from eight European countries composed of existing biorepositories from expert centers (n = 285).
Results: IgG from pediatric AIH patients exhibited increased polyreactivity to multiple protein and non-protein substrates compared to non-AIH liver diseases and healthy children. pIgG had an AUC of 0.900 to distinguish AIH from non-AIH liver diseases. pIgG had a 31-73% higher specificity than ANA and anti-SMA and comparable sensitivity that was 6-20 times higher than of anti-SLA/LP, anti-LC1 and anti-LKM. pIgG had a 21-34% higher accuracy than conventional autoantibodies, was positive in 43-75% of children with AIH and normal IgG and independent from treatment response.
Conclusion: Detecting pIgG improves the diagnostic evaluation of pediatric AIH compared to conventional autoantibodies, primarily owing to higher accuracy and specificity.
(© 2024. The Author(s).)
Databáze: MEDLINE
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