Complementary use of autoantibody detection methods facilitates diagnosis of juvenile autoimmune hepatitis and autoimmune sclerosing cholangitis
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background & Aims: The diagnosis of juvenile autoimmune hepatitis (AIH) is challenging given its heterogeneous presentation. Autoantibodies, typically detected by immunofluorescence testing (IFT), together with liver histology, represent key diagnostic features. Polyreactive immunoglobulin G (pIgG) has recently emerged as a complementary biomarker in AIH. This retrospective multicentre study aimed to compare ELISA-based autoantibody testing and IFT on HEp-2 cells with the gold standard of IFT on rodent tissue sections in children with autoimmune and non-autoimmune liver diseases. Methods: Autoantibody detection was performed centrally at Hannover Medical School using three commercial antinuclear antibody (ANA) ELISAs, one commercial F-actin ELISA, one in-house pIgG ELISA, and IFT on HEp-2 cells, in comparison to the gold standard of IFT on rodent tissue sections. Samples from children with AIH (n = 69), autoimmune sclerosing cholangitis (AISC; n = 13) and other liver diseases (n = 120) were analysed from nine European centres. Results: The AUCs for the detection of AIH/AISC were moderate to good for ANA detection by IFT (gold standard of rodent tissue AUC: 0.748; HEp-2 AUC: 0.756) and were comparable to ELISA-based detection (0.622-0.772). Anti-smooth muscle antibody (SMA) IFT on rodent tissue yielded an AUC of 0.694. Specificity was increased to 100% by including the SMA staining pattern of vessels, glomeruli and tubules. ELISA-based quantification of anti-F-actin (AUC = 0.868) and pIgG (AUC = 0.844) showed the highest AUCs. While the majority of F-actin-positive children were pIgG-positive (80.3%), pIgG was also detected in 52.4% of F-actin-negative children with AIH. Conclusion: ELISA-based assays provide reliable ANA detection comparable to IFT. Anti-F-actin and pIgG ELISAs showed the highest accuracy for predicting juvenile AIH/AISC and may complement existing diagnostic criteria. Impact and implications: Autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC) are rare paediatric liver diseases that can be difficult to distinguish from other hepatopathies. Autoantibody testing is central to diagnosis, yet paediatric performance across platforms has been poorly standardised and sparsely reported. In this multicentre comparison (202 sera from nine expert centres across eight European countries), indirect immunofluorescence (IFT) on rodent tissue showed suboptimal discrimination at the commonly advocated 1:20 cut-off, whereas accuracy for ANA and SMA improved markedly at 1:320. ANA detection by IFT on HEp-2 cells and by ELISA was comparable to rodent tissue IFT. ELISAs for F-actin and pIgG achieved the highest AUCs for identifying AIH/AISC and may complement current diagnostics. Substantial inter-platform discordance for ANA underscores the need for harmonisation. Collectively, these data support the use of multiple validated platforms with platform-appropriate cut-offs in paediatric AIH/AISC serology and support updates to diagnostic algorithms to improve diagnostic timeliness and reliability.
Source: JHEP Reports
Authors: Theresa Kirchner, Norman Junge, Nicole Henjes, Stephanie Loges, Muhammed Yuksel, Wojciech Janczyk, Claudine Lalanne, Kalliopi Zachou, Ye H. Oo, Jérôme Gournay, Simon Pape, Joost PH. Drenth, Amédée Renand, George N. Dalekos, Luigi Muratori, Piotr Socha, Cigdem Arikan, Yun Ma, Heiner Wedemeyer, Ulrich Baumann, Bastian Engel, Richard Taubert
Institutions: Medizinische Hochschule Hannover, ERN RARE-LIVER, Koç University, King's College London, King's College Hospital, Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi, Children's Memorial Health Institute, University of Bologna, University Hospital of Larissa, General Hospital of Larisa, Greece, University Hospitals Birmingham NHS Foundation Trust, NIHR Birmingham Biomedical Research Centre, Inserm, Centre Hospitalier Universitaire de Nantes, Centre d'Investigation Clinique de Nantes, Nantes Université, Radboud University Medical Center, Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, Center for Research in Transplantation and Translational Immunology, Université de Nantes
Language: English
Topic: Liver Diseases and Immunity
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,110
Funders: Sir Jules Thorn Charitable Trust, Royal College of Physicians, Deutsche Forschungsgemeinschaft, Institut National de la Santé et de la Recherche Médicale, Radboud Universiteit, Else Kröner-Fresenius-Stiftung, Medizinischen Hochschule Hannover, Radboud Universitair Medisch Centrum, Niedersächsisches Ministerium für Wissenschaft und Kultur, Birmingham Biomedical Research Centre, Euroimmun Medizinische Labordiagnostika
OpenAlex ID: W4417080350