Neutralising autoantibodies against IL-10 and HLA-DRB1*01:03 in paediatric patients with inflammatory bowel disease
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Interleukin-10 (IL-10) is an essential regulator of intestinal immune homeostasis. Neutralising autoantibodies against IL-10 (anti-IL-10) have been identified in children and also adult patients with IBD. Positivity for anti-IL-10 autoantibodies was associated with carriage of HLA-DRB1*01:03 allele. OBJECTIVE: To determine the prevalence of anti-IL-10 in paediatric IBD and assess the associated clinical phenotype. DESIGN: We conducted a cross-sectional multicentre study across paediatric IBD cohorts from four countries. Anti-IL-10 antibodies were investigated in serum and plasma from paediatric patients with IBD (mean age of IBD onset 11.2±3.8 years). IL-10-neutralisation capacity was confirmed by functional IL-10 reporter assay, competitive ELISA and cytokine release assay. Clinical data were analysed to evaluate disease phenotype and treatment outcomes, with comparison with matched controls. HLA-DRB1*01:03 analysis was performed. RESULTS: Anti-IL-10 positivity was identified in 26/1045 paediatric patients with IBD (2.5%) (Crohn's disease n=6, UC n=19, IBD unclassified n=1; IBD diagnosis age of 13±3 years). Anti-IL-10 autoantibodies were of the IgG class and amplified pro-inflammatory cytokine responses in vitro. Anti-IL-10-positive patients exhibited more severe disease compared with matched controls, including an increased prevalence of difficult-to-treat disease (23% vs 6%, p=0.03), higher rate of acute severe UC (26% vs 6%; p=0.038) and higher rates of colectomy (27% vs 6%, p=0.01). Eighty percent (16/20) of anti-IL-10-positive patients with available HLA data carried the HLA-DRB1*01:03 allele, compared with 1.5% in the anti-IL-10-negative group. CONCLUSION: Anti-IL-10 autoantibodies are present in a subgroup of paediatric patients with IBD and are associated with difficult-to-treat disease.
Source: Gut
Authors: Nima Gharahdaghi, Pai-Jui Yeh, Katherine Vadakethala, Madeleine Coy, Ladan Kabiri, Bushra Naz, Chamara Jayamanne, Linn Hansson, Viktor Zouboulis, Astor Rodrigues, Lucy Howarth, Fatimah Alqahtani, Arya Ghate, Fernando Vázquez López, Zachary Green, Robert M Beattie, Marco Gasparetto, Natalia Nedelkopoulou, Ashrita Iyengar, Amrit Gopan, Nicholas M Croft, Carla Grimaldi, Jochen Kammermeier, Kelsey Jones, Danielle M H Barendregt, Mian Chen, Martin Barnardo, Qian Zhang, Laura Fachal, Carl A Anderson, Anna Adams, Hazel Johnson, Hannah Gordon, Noa Tal, Elizabeth Renji, David C Wilson, Paul Henderson, Rafeeq Muhammed, Kwang Yang Lee, Akshay Kapoor, Rachel Levi, Matthias Zilbauer, Anne M Griffiths, Dan Turner, Sophie Hambleton, Rainer Doffinger, Janneke N Samsom, UK PIBD BioResource, Miles Parkes, Simon P Travis, Dror S Shouval, Lissy de Ridder, Aleixo Muise, Scott B Snapper, James J Ashton, Sarah Ennis, Holm H Uhlig
Institutions: Centre for Human Genetics, University of Oxford, Chang Gung Memorial Hospital, Linkou Chang Gung Memorial Hospital, Oxford University Hospitals NHS Trust, University of Southampton, Southampton Children's Hospital, University of East Anglia, Norfolk and Norwich University Hospital, Boston Children's Hospital, Hospital for Sick Children, Queen Mary University of London, Barts Health NHS Trust, Blizard Institute, Evelina London Children's Healthcare, Great Ormond Street Hospital, Erasmus MC, Wellcome Sanger Institute, Tel Aviv University, Schneider Children's Medical Center, Alder Hey Children's Hospital, Centre for Inflammation Research, University of Edinburgh, Birmingham Children's Hospital, Bristol Royal Hospital for Children, Sheffield Children's NHS Foundation Trust, Sheffield Children's Hospital, Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, Addenbrooke's Hospital, Hebrew University of Jerusalem, Shaare Zedek Medical Center, Bikur Cholim Hospital, Newcastle University, Cambridge University Hospitals NHS Foundation Trust, National Institute for Health and Care Research, NIHR Cambridge Biomedical Research Centre, Kennedy Institute of Rheumatology, Leiden University Medical Center
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7202209588