Researchers at the Nuffield Department of Medicine, University of Oxford, along with Newcastle University's Translational and Clinical Research Institute and the Department of Immunology at Cambridge University Hospitals NHS Foundation Trust, announced on June 10 that they have identified an important driver of inflammatory bowel disease (IBD). The discovery may reshape understanding of IBD and could lead to targeted approaches for diagnosis and treatment in a subset of patients.
The study, published in the New England Journal of Medicine, analyzed over 4,900 patients with IBD. Researchers found that a substantial subset showed autoimmune responses to interleukin-10 (IL-10), which leads to uncontrolled inflammation. They also discovered that this damaging immune response is the mechanism behind one of the strongest known genetic risk factors for IBD.
Antibodies blocking IL-10 remove one of the body's natural controls on inflammation, allowing it to continue unchecked. The researchers detected high levels of anti-IL10 neutralizing autoantibodies in about 3.5% of IBD patients but not in healthy individuals. This could represent up to 20,000 people with IBD in the UK carrying these autoantibodies. The presence was strongly linked to carriage of a particular genetic variant known as HLA-DRB1*01:03.
Professor Holm Uhlig said, "We've suspected an important role of interleukin 10 in patients with inflammatory bowel disease for decades. The study now provides clear evidence and contributes the missing link between a well-known genetic variant that had been linked to severe inflammatory bowel disease in the past and the very recently discovered autoimmunity to interleukin 10." Uhlig added, "Understanding what drives the inflammation provides a clear explanation for disease in this group of people and opens the door to new treatments that target the autoantibodies themselves or cells that produce those autoantibodies."
Sophie Hambleton said, "This discovery shows how the study of rare, inherited disorders can shed new light on common conditions. The groundwork was laid over 10 years ago when genetic defects in IL-10 or its receptor were found in young children with severe IBD. Later, we realised that neutralising autoantibodies against IL-10 were mimicking this effect in 2 little girls with colitis." Dr Rainer Doffinger said, "By identifying patients early and giving them targeted treatment, we could reduce reliance on expensive ongoing therapy and prevent complications. Even modest reductions in biologic treatment, admissions and surgery could translate into savings of many millions of pounds annually for the NHS, alongside major benefits for patients through fewer interventions, improved quality of life or even durable remission."
