Journal Article

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

Arikan, Cigdem, Jaeckel, Elmar, Loges, Stephanie, Lalanne, Claudine, Engel, Bastian, Taubert, Richard, Ma, Yun, Gournay, Jérôme, Dalekos, George N., Diestelhorst, Jana, Hupa-Breier, Katharina Luise, Zachou, Kalliopi, Janczyk, Wojciech, Pape, Simon, Muratori, Luigi, Wedemeyer, Heiner, Oo, Ye H., Henjes, Nicole, Renand, Amédée, Drenth, Joost P. H., Socha, Piotr, Junge, Norman, Kirchner, Theresa, Baumann, Ulrich, Manns, Michael P., Yuksel, Muhammed

2024

Overview

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. Graphical Abstract

• Publisher: Springer India,Springer Nature B.V,Springer Internat. Publ
• Subject: Adolescent / Animal tissues / Animals / Antibodies / Antigens / Antinuclear antibodies / Autoantibodies / Autoantibodies - blood / Autoantibodies - immunology / Child / Child, Preschool / Children / Cholangitis / Colorectal Surgery / Enzyme-linked immunosorbent assay / Enzyme-Linked Immunosorbent Assay - methods / Ethics / Female / Hepatitis / Hepatitis, Autoimmune - blood / Hepatitis, Autoimmune - diagnosis / Hepatitis, Autoimmune - immunology / Hepatology / Humans / IgG antibody / Immunofluorescence / Immunoglobulin G / Immunoglobulin G - blood / Immunoglobulin G - immunology / Immunoglobulins / Life Sciences / Liver / Liver diseases / Male / Medical diagnosis / Medical schools / Medicine / Medicine & Public Health / Metabolism / Original / Original Article / Pediatrics / Proteins / Retrospective Studies / Sensitivity and Specificity / Smooth muscle / Surgery