Neutralising autoantibodies against IL-10 and HLA-DRB1*01:03 in paediatric patients with inflammatory bowel disease.
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Gharahdaghi Nima, Yeh Pai-Jui, Vadakethala Katherine, Coy Madeleine, Kabiri Ladan, Naz Bushra, Jayamanne Chamara, Hansson Linn, Zouboulis Viktor, Rodrigues Astor, Howarth Lucy, Alqahtani Fatimah, Ghate Arya, Vázquez López Fernando, Green Zachary, Beattie Robert M, Gasparetto Marco, Nedelkopoulou Natalia, Iyengar Ashrita, Gopan Amrit, Croft Nicholas M, Grimaldi Carla, Kammermeier Jochen, Jones Kelsey, Barendregt Danielle M H, Chen Mian, Barnardo Martin, Zhang Qian, Fachal Laura, Anderson Carl A, Adams Anna, Johnson Hazel, Gordon Hannah, Tal Noa, Renji Elizabeth, Wilson David C, Henderson Paul, Muhammed Rafeeq, Lee Kwang Yang, Kapoor Akshay, Levi Rachel, Zilbauer Matthias, Griffiths Anne M, Turner Dan, Hambleton Sophie, Doffinger Rainer, Samsom Janneke N, UK PIBD BioResource, Parkes Miles, Travis Simon P, Shouval Dror S, de Ridder Lissy, Muise Aleixo, Snapper Scott B, Ashton James J, Ennis Sarah, Uhlig Holm H
Аннотация
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.