Gut · 2026
IL-10-neutralising autoantibodies in paediatric-onset inflammatory bowel disease.
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Yalcinkaya Ahmet, Sandström Ella, Degrace Emma J, Pigneur Benedicte, Abi-Nader Elie, Berrebi Dominque, Duclaux-Loras Rémi, Nancey Stéphane, Collardeau-Frachon Sophie, Gornet Jean-Marc, Bertheau Philippe, Tolin Hernani Maria Del Mar, Dumaine Anne, Jabri Bana, Ruemmele Frank M, Cerf-Bensussan Nadine, Parlato Marianna, Charbit-Henrion Fabienne, Landegren Nils
Аннотация
BACKGROUND: Autoantibodies neutralising interleukin-10 (IL-10) have recently been described as a mechanism of inflammatory bowel disease (IBD); however, prevalence and clinical impacts are unknown.
OBJECTIVE: To determine the prevalence and longitudinal persistence of IL-10 autoantibodies in a population of paediatric-onset IBD and to assess associated clinical features.
DESIGN: We analysed plasma IL-10 autoantibodies with a cross-sectional study of a paediatric cohort of patients diagnosed with either IBD (n=239), autoimmune enteropathy (n=37) or congenital diarrhoea and enteropathies (n=42). Functional testing to assess IL-10 response was performed using cell-based assays under biologically relevant stimulation.
RESULTS: Five patients with autoantibodies neutralising 2.5 ng/mL of IL-10 were identified, three of whom were also neutralising at 5 ng/mL. All had IBD without a known monogenic cause. Longitudinal samples (available in three of five subjects) showed autoantibody persistence in two cases, 3 and 9 years after baseline. The patient without persistence had undergone haematopoietic stem-cell transplantation (HSCT) 2 years after baseline sampling. The prevalence of neutralising IL-10 autoantibodies was 2.1% (95% CI 0.7% to 4.8%), while the frequency was 2.6% in subjects without IBD-associated monogenic variants (n=192).
CONCLUSION: In paediatric autoimmune and inflammatory gut diseases, IL-10 neutralising autoantibodies were detected only among patients with IBD without known genetic aetiology. Patients had heterogeneous clinical characteristics and IL-10 autoantibodies persisted under standard immunosuppressive treatment but disappeared following HSCT and may have declined with colectomy or ileostomy. Screening for IL-10 autoantibodies via functional assays may identify a subgroup of patients with distinct aetiology and therapeutic needs.
OBJECTIVE: To determine the prevalence and longitudinal persistence of IL-10 autoantibodies in a population of paediatric-onset IBD and to assess associated clinical features.
DESIGN: We analysed plasma IL-10 autoantibodies with a cross-sectional study of a paediatric cohort of patients diagnosed with either IBD (n=239), autoimmune enteropathy (n=37) or congenital diarrhoea and enteropathies (n=42). Functional testing to assess IL-10 response was performed using cell-based assays under biologically relevant stimulation.
RESULTS: Five patients with autoantibodies neutralising 2.5 ng/mL of IL-10 were identified, three of whom were also neutralising at 5 ng/mL. All had IBD without a known monogenic cause. Longitudinal samples (available in three of five subjects) showed autoantibody persistence in two cases, 3 and 9 years after baseline. The patient without persistence had undergone haematopoietic stem-cell transplantation (HSCT) 2 years after baseline sampling. The prevalence of neutralising IL-10 autoantibodies was 2.1% (95% CI 0.7% to 4.8%), while the frequency was 2.6% in subjects without IBD-associated monogenic variants (n=192).
CONCLUSION: In paediatric autoimmune and inflammatory gut diseases, IL-10 neutralising autoantibodies were detected only among patients with IBD without known genetic aetiology. Patients had heterogeneous clinical characteristics and IL-10 autoantibodies persisted under standard immunosuppressive treatment but disappeared following HSCT and may have declined with colectomy or ileostomy. Screening for IL-10 autoantibodies via functional assays may identify a subgroup of patients with distinct aetiology and therapeutic needs.