In a study of more than 4,900 people with IBD, scientists found that approximately 3.5% of patients produce antibodies that interfere with interleukin-10 (IL-10), a protein that helps prevent excessive inflammation. These antibodies were detected in people with both Crohn's disease and ulcerative colitis, but not in healthy individuals. Based on the prevalence of IBD in the UK, researchers estimate that 15,000 to 20,000 patients nationwide could carry these harmful antibodies.
Under normal circumstances, IL-10 acts as a chemical messenger that helps the immune system regulate inflammation. When the antibodies block its activity, the body loses one of its built-in safeguards against excessive immune responses, allowing inflammation to persist.
The investigation also revealed a strong association between the IL-10-blocking antibodies and a genetic variant called HLA-DRB101:03. Scientists at Oxford first connected this variant to a severe form of inflammatory bowel disease 30 years ago, but the biological process linking the gene to the condition had remained unclear. People who carry HLA-DRB101:03 are substantially more likely to develop the IL-10-interfering antibodies.
Professor Holm Uhlig, a pediatric gastroenterologist and director of the Centre for Human Genetics at Oxford's Nuffield Department of Medicine, 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. 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."
The findings build on research into rare inherited disorders that disrupt the body's ability to control inflammation. Sophie Hambleton, professor of pediatrics and immunology at Newcastle University, noted: "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 realized that neutralizing autoantibodies against IL-10 were mimicking this effect in 2 little girls with colitis."
Beyond explaining a mysterious cause of intestinal inflammation, the discovery could lead to a blood test that identifies people whose disease is associated with antibodies against IL-10. Dr. Rainer Doffinger, a clinical immunologist at Cambridge University Hospitals NHS Foundation Trust, 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 the major benefits for patients through fewer interventions, improved quality of life or even durable remission."
Professor Simon Travis, professor of clinical gastroenterology at the University of Oxford and the Kennedy Institute of Rheumatology, called it "the most exciting discovery in a lifetime specialising in IBD. It means that we can now identify a group where we know what is causing the disease and that creates a real opportunity to change how we manage this disease."