Healthcare (Commonwealth Union) – Inflammatory bowel disease (IBD) is a condition known to be a key obstacle for an individual’s daily activities by impacting the digestive system.
Scientists from the Nuffield Department of Medicine at the University of Oxford, working alongside Newcastle University’s Translational and Clinical Research Institute and the Department of Immunology at Cambridge University Hospitals NHS Foundation Trust, have identified a key factor that drives IBD. Their discovery significantly alters current understanding of the condition and could pave the way for more precise diagnostic tools and personalised treatments for certain patient groups. The research also indicates that IBD is not a single illness, but rather a collection of biologically distinct disorders caused by different underlying processes.
Published in the New England Journal of Medicine, the study examined more than 4,900 individuals with IBD and uncovered two major findings. First, a notable subset of patients develops autoimmune reactions against interleukin-10 (IL-10), a critical regulator of the immune system, resulting in excessive and uncontrolled inflammation. Second, this harmful immune response appears to explain one of the strongest genetic risk factors associated with IBD.
Normally, IL-10 acts as a key anti-inflammatory messenger that helps keep the immune system in balance. However, in affected patients, antibodies that neutralise IL-10 effectively disable this protective “braking system,” allowing inflammatory activity to persist without restraint.
IBD—comprising Crohn’s disease and ulcerative colitis—affects approximately millions across the world. It is a chronic condition that often begins in adolescence or early adulthood and may require ongoing medical care, long-term use of immune-suppressing drugs, and sometimes surgical intervention. Although treatments have improved, many patients still move between therapies without achieving sustained control of the disease, placing a significant burden on both individuals and healthcare systems.
Researchers identified elevated levels of anti-IL10 neutralising autoantibodies in the bloodstream of roughly 3.5% of people with inflammatory bowel disease, including those with Crohn’s disease and ulcerative colitis, but these antibodies were absent in healthy individuals. This suggests that an estimated 15,000–20,000 IBD patients in the UK may carry them.
They also discovered a strong association between these antibodies and a specific genetic variant, HLA-DRB1*01:03.
This gene variant had previously been linked to severe inflammatory bowel disease by Oxford scientists around three decades ago. The latest findings indicate that individuals carrying HLA-DRB1*01:03 are much more prone to producing antibodies that inhibit IL-10, offering a clearer explanation of how this genetic factor contributes to disease development.
Professor Holm Uhlig, Paediatric Gastroenterologist and Director of the Centre for Human Genetics at the Nuffield Department of Medicine, University of Oxford, and senior author of the study, indicated that they have long suspected that interleukin-10 plays a key role in inflammatory bowel disease. This research now provides strong evidence and bridges the gap between a well-established genetic risk factor for severe IBD and the recently identified autoimmunity against interleukin-10.
He further pointed out that gaining knowledge of what drives the inflammation, gives a clear reason for disease in this group of individuals and paves the way for new treatments that target the autoantibodies themselves or cells forming those autoantibodies.’ Top of Form
Sophie Hambleton, Professor of Paediatrics and Immunology at Newcastle University, says “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.”
The scientists engaged in the study suggest that the findings could pave the way for a blood test to detect this subgroup of patients, enabling clinicians to quickly select more suitable treatment options.
