A study, published by the New England Journal of Medicine, has identified a new disease-inducing mechanism for inflammatory bowel disease (IBD) in which the immune system attacks its own regulatory function.
Interleukin-10 (IL10) is an anti-inflammatory protein that crucially controls intestinal immunity. Children with genetic defects in IL10 or its receptors, suffer from a severe form of IBD that typically presents within the first few months of life. Symptoms are acute and include bloody diarrhoea and severe abdominal pain.
This research, a collaboration between the Great North Children’s Hospital, Cambridge University Hospital, and the universities of Cambridge, Newcastle and Oxford, identified self-directed antibodies that attack IL10 in two patients with early onset severe IBD. These antibodies prevented IL10 from binding to its receptor and so caused an increased inflammatory response.
As a consequence of identifying the autoantibodies, one patient received treatment to suppress antibody production, leading to eventual disappearance of the anti-IL10 autoantibodies, and resolution of IBD.
Neutralizing autoantibodies against IL-10 in Inflammatory Bowel Disease, was a collaboration between teams led by Dr Rainer Döffinger, from Addenbrookes Hospital, Cambridge; Professor Sophie Hambleton at Newcastle University and the Great North Children’s Hospital; and Professor Holm Uhlig, at the University of Oxford.
This research was supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (BRC) and NIHR Oxford BRC, and by The Leona M. and Harry B. Helmsley Charitable Trust. It was funded in part by the Wellcome Trust.
Read the full paper here: Autoimmunity against anti-inflammatory regulator IL10 in inflammatory bowel disease. Griffin et al. NEJM 2024