A groundbreaking study published today reveals a new disease-inducing mechanism for inflammatory bowel disease (IBD), where the immune system sabotages its own regulatory functions.
Interleukin-10 (IL10), an essential anti-inflammatory protein, plays a pivotal role in regulating intestinal immunity.
Children with genetic defects in IL10 or its receptors suffer from a severe form of IBD, usually presenting in the first few months of life with acute symptoms like bloody diarrhoea and severe abdominal pain.
This collaborative research, involving the Great North Children’s Hospital and the universities of Cambridge, Newcastle, and Oxford, uncovered self-directed antibodies targeting IL10 in two patients with early-onset severe IBD.
These antibodies hinder IL10 from binding to its receptor, thereby amplifying the inflammatory response.
Following this discovery, one patient received treatment to suppress antibody production, leading to the eventual disappearance of the anti-IL10 autoantibodies and the resolution of IBD symptoms.
The study, titled “Neutralising Autoantibodies against IL-10 in Inflammatory Bowel Disease,” was published in the New England Journal of Medicine.
It represents a collaboration between Dr. Rainer Döffinger of 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.
Dr. Rainer Döffinger, Consultant Clinical Scientist at Cambridge University Hospitals, remarked, “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.”
Professor Sophie Hambleton, from Newcastle University, added, “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.”
Professor Holm Uhlig of the University of Oxford stated, “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 received support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (BRC) and NIHR Oxford BRC, as well as funding from The Leona M. and Harry B. Helmsley Charitable Trust and the Wellcome Trust.