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

  • UK PIBD BioResource
  • , Miles Parkes
  • , Simon P. Travis
  • , Dror S. Shouval
  • , Lissy de Ridder
  • , Alexio Muise
  • , Scott B. Snapper
  • , James J. Ashton
  • , Sarah Ennis
  • , Holm H. Uhlig

Research output: Contribution to journalArticlepeer-review

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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.
Original languageEnglish
Article numberPMID 42580871
Pages (from-to)1-11
JournalGut
DOIs
Publication statusPublished - 11 Aug 2026

Keywords

  • Auto-antibodies
  • Cytokines
  • IBD
  • Interleukins

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