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Neutralising autoantibodies against IL-10 and HLA-DRB1*01:03 in paediatric patients with inflammatory bowel disease

Lookup NU author(s): Professor Sophie HambletonORCiD

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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.

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Author(s): Gharahdaghi N, Yeh PJ, Vadakethala K, Coy M, Kabiri L, Naz B, Jayamanne C, Hansson L, Zouboulis V, Rodrigues A, Howarth L, Alqahtani F, Ghate A, Vázquez López F, Green Z, Beattie RM, Gasparetto M, Nedelkopoulou N, Iyengar A, Gopan A, Croft NM, Grimaldi C, Kammermeier J, Jones K, Barendregt DMH, Chen M, Barnardo M, Zhang Q, Fachal L, Anderson CA, Adams A, Johnson H, Gordon H, Tal N, Renji E, Wilson DC, Henderson P, Muhammed R, Lee KY, Kapoor A, Levi R, Zilbauer M, Griffiths AM, Turner D, Hambleton S, Doffinger R, Samsom JN, UK PIBD BioResource, Parkes M, Travis SP, Shouval DS, de Ridder L, Muise A, Snapper SB, Ashton JJ, Ennis S, Uhlig HH

Publication type: Article

Publication status: Published

Journal: Gut

Year: 2026

Pages: epub ahead of print

Online publication date: 11/08/2026

Acceptance date: 30/07/2026

Date deposited: 09/09/2026

ISSN (print): 0017-5749

ISSN (electronic): 1468-3288

Publisher: BMJ Group

URL: https://doi.org/10.1136/gutjnl-2026-339329

DOI: 10.1136/gutjnl-2026-339329

Data Access Statement: Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. De-identified data that support the findings of this study are available from the corresponding author on reasonable request, subject to institutional approvals, ethical regulations and data-sharing agreements.

PubMed id: 42580871

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