A ground-breaking study 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 Hospitals, and the universities of Cambridge, Newcastle and Oxford, identified self-directed antibodies that attack IL10 in two patients with early onset severe IBD. Scientists discovered that these antibodies prevented IL10 from binding to its receptor and so caused an increased inflammatory response.
As a consequence of this discovery, one patient received treatment to suppress antibody production, leading to eventual disappearance of the anti-IL10 autoantibodies, and resolution of IBD.
The paper, published in the New England Journal of Medicine, 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.
Rainer Döffinger, Consultant Clinical Scientist of the Department of Clinical Biochemistry and Immunology at Cambridge University Hospitals, said: “This discovery adds to a growing body of evidence showing the severe consequences when the body’s immune defence is attacking itself. The study is the result of cutting-edge NHS diagnostics and a great and efficient collaboration between the centres to deliver results with real-world implications for new therapies, that will ease the burden of suffering in patients with IBD.”
Sophie Hambleton, Professor of Paediatrics and Immunology at Newcastle University, and honorary consultant paediatrician at The Newcastle upon Tyne Hospitals NHS Foundation Trust, said: “Here, we drew upon knowledge of genetic forms of IBD to uncover a new and unexpected molecular mechanism for disease. This understanding informed our choice of therapy, an example of precision medicine in action.”
Holm Uhlig, Professor of Paediatric Gastroenterology at the University of Oxford, said: “While there is abundant evidence that genetic and environmental factors are a cause of IBD, the results of our joint study draw attention to autoimmunity towards the immunoregulatory cytokine IL10. This research may have wider implications for patients beyond infancy and I am grateful for the incredible collaborative effort that made it possible.”
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.