{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden",
        "Science for Life Laboratory (SciLifeLab), Uppsala University, Uppsala, Sweden"
      ],
      "name": "Ahmet Yalcinkaya"
    },
    {
      "affiliations": [
        "Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden",
        "Science for Life Laboratory (SciLifeLab), Uppsala University, Uppsala, Sweden"
      ],
      "name": "Ella Sandström"
    },
    {
      "affiliations": [
        "Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden",
        "Science for Life Laboratory (SciLifeLab), Uppsala University, Uppsala, Sweden"
      ],
      "name": "Emma J Degrace"
    },
    {
      "affiliations": [
        "Universite Paris Cite, Paris, France",
        "Department of Pediatric Gastroenterology, Assistance Publique - Hôpitaux de Paris, Paris, France"
      ],
      "name": "Benedicte Pigneur"
    },
    {
      "affiliations": [
        "Universite Paris Cite, Paris, France",
        "Department of Pediatric Gastroenterology, Assistance Publique - Hôpitaux de Paris, Paris, France"
      ],
      "name": "Elie Abi-Nader"
    },
    {
      "affiliations": [
        "Universite Paris Cite, Paris, France",
        "Tissue Immunity in Homeostasis and Disease, Inserm UMR1163, Paris, France"
      ],
      "name": "Dominque Berrebi"
    },
    {
      "affiliations": [
        "International Center for Research in Infectiology, UMR5308, Lyon, France",
        "Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Rémi Duclaux-Loras"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Hôpital Lyon Sud, Pierre-Bénite, France"
      ],
      "name": "Stéphane Nancey"
    },
    {
      "affiliations": [
        "Department of Pathology, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Sophie Collardeau-Frachon"
    },
    {
      "affiliations": [
        "Universite Paris Cite, Paris, France",
        "Department of Gastroenterology, Assistance Publique - Hopitaux de Paris, Paris, France"
      ],
      "name": "Jean-Marc Gornet"
    },
    {
      "affiliations": [
        "Universite Paris Cite, Paris, France",
        "Department of Pathology, Assistance Publique - Hopitaux de Paris, Paris, France"
      ],
      "name": "Philippe Bertheau"
    },
    {
      "affiliations": [
        "Digestive, Hepatology and Paediatric Nutrition Unit, Infant Maternal Hospital, Hospital General Universitario Gregorio Maranon, Madrid, Spain"
      ],
      "name": "Maria del Mar Tolin Hernani"
    },
    {
      "affiliations": [
        "Tissue Immunity in Homeostasis and Disease, Inserm UMR1163, Paris, France"
      ],
      "name": "Anne Dumaine"
    },
    {
      "affiliations": [
        "Department of Pediatric Gastroenterology, Assistance Publique - Hôpitaux de Paris, Paris, France",
        "Tissue Immunity in Homeostasis and Disease, Inserm UMR1163, Paris, France"
      ],
      "name": "Bana Jabri"
    },
    {
      "affiliations": [
        "Department of Pediatric Gastroenterology, Assistance Publique - Hôpitaux de Paris, Paris, France",
        "Tissue Immunity in Homeostasis and Disease, Inserm UMR1163, Paris, France"
      ],
      "name": "Frank M Ruemmele"
    },
    {
      "affiliations": [
        "Intestinal Immunity, Inserm UMR1163, Paris, France",
        "Genomic Medicine for Rare Diseases, Assistance Publique - Hôpitaux de Paris, Paris, France"
      ],
      "name": "Nadine Cerf-Bensussan"
    },
    {
      "affiliations": [
        "Tissue Immunity in Homeostasis and Disease, Inserm UMR1163, Paris, France",
        "Intestinal Immunity, Inserm UMR1163, Paris, France"
      ],
      "name": "Marianna Parlato"
    },
    {
      "affiliations": [
        "Intestinal Immunity, Inserm UMR1163, Paris, France",
        "Genomic Medicine for Rare Diseases, Assistance Publique - Hôpitaux de Paris, Paris, France"
      ],
      "name": "Fabienne Charbit-Henrion"
    },
    {
      "affiliations": [
        "Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden",
        "Science for Life Laboratory (SciLifeLab), Uppsala University, Uppsala, Sweden"
      ],
      "name": "Nils Landegren"
    }
  ],
  "title": "IL-10-neutralising autoantibodies in paediatric-onset inflammatory bowel disease",
  "uid": "8108be2e-ce23-5025-b8aa-6e9ff842195a"
}