Scientists from the University of Oxford, Newcastle University, and Cambridge University Hospitals NHS Foundation Trust have identified a previously unknown cause of inflammatory bowel disease. The findings appear in the New England Journal of Medicine.
The researchers examined more than 4,900 people with IBD and found that approximately 3.5% produced antibodies that neutralize interleukin-10 (IL-10), a protein that prevents excessive inflammation. These antibodies were detected in patients with both Crohn's disease and ulcerative colitis, but not in healthy individuals. Based on UK prevalence rates, researchers estimate 15,000 to 20,000 patients nationwide carry these harmful antibodies.
The discovery resolves a 30-year mystery. Scientists at Oxford first linked a genetic variant called HLA-DRB1*01:03 to severe IBD three decades ago, but the biological mechanism remained unclear. The new results show that people carrying this variant are substantially more likely to develop antibodies that interfere with IL-10, explaining how the genetic risk factor contributes to intestinal inflammation.
The findings build on over a decade of research into rare inherited disorders affecting inflammation control. Sophie Hambleton, Professor of Pediatrics and Immunology at Newcastle University, stated, "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."
Researchers believe the results could enable a blood test identifying patients whose IBD involves IL-10-blocking antibodies. Such testing could allow doctors to select targeted treatments addressing the underlying immune malfunction rather than relying on trial-and-error therapy.
Dr. Rainer Doffinger at Cambridge University Hospitals noted potential healthcare benefits. "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 from the University of Oxford called this "the most exciting discovery in a lifetime specialising in IBD" because identifying a specific biological cause creates opportunities to change disease management.