We discovered high-titer neutralizing autoantibodies against interleukin-10 in a child with infantile-onset inflammatory bowel disease (IBD), a phenocopy of inborn errors of interleukin-10 signaling. After B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn. A second child with neutralizing anti-interleukin-10 autoantibodies had a milder course of IBD and has been treated without B-cell depletion. We conclude that neutralizing anti-interleukin-10 autoantibodies may be a causative or modifying factor in IBD, with potential implications for therapy. (Funded by the National Institute for Health and Care Research and others.).
Journal article
The New England journal of medicine
08/2024
391
434 - 441
From the Immunity and Inflammation Theme, Newcastle University Translational and Clinical Research Institute (H.G., S.H.), and the Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust (P.S.L., E.W., A.M., A.J.C., S.H.), Newcastle upon Tyne, the Department of Clinical Biochemistry and Immunology, Cambridge University Hospital (L.C.-G., S.E., S.D., R.D.), and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (R.D.), Cambridge, the Translational Gastroenterology Unit (N.G., S.T., P.K., H.H.U.), the Kennedy Institute of Rheumatology (S.T.), the NIHR Oxford Biomedical Research Centre (S.T., P.K., H.H.U.), and the Department of Pediatrics (H.H.U.), University of Oxford, Oxford, the Department of Pediatric Gastroenterology, Royal Belfast Hospital for Sick Children (A.S., L.M.), and the Department of Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust (S.I.), Belfast, and the Department of Pediatric Gastroenterology, Royal Aberdeen Children's Hospital, Aberdeen (S.B.) - all in the United Kingdom; and the Pediatric Gastroenterology Department, Pál Heim National Pediatric Institute, Budapest, Hungary (A.S.).
B-Lymphocytes, Humans, Inflammatory Bowel Diseases, Immunoglobulins, Intravenous, Interleukin-10, Autoantibodies, Glucocorticoids, Treatment Outcome, Drug Therapy, Combination, Severity of Illness Index, Child, Preschool, Infant, Female, Male, Antibodies, Neutralizing, Infliximab