Decades old puzzle solved as scientists uncover cause of inflammatory bowel disease

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Oxford, UK, 10 June 2026: Researchers at the Nuffield Department of Medicine, University of Oxford, together with Newcastle University’s Translational and Clinical Research Institute and the Department of Immunology at Cambridge University Hospitals NHS Foundation Trust, have identified an important driver of inflammatory bowel disease (IBD). This discovery reshapes understanding of IBD and opens the way to targeted approaches to diagnosis and treatment in a subset of patients. The findings suggest that inflammatory bowel disease is not a single condition, but a group of biologically distinct diseases driven by different underlying mechanisms.

In a study published today in the New England Journal of Medicine, researchers analysed over 4,900 patients with IBD and made two major discoveries: first, that a substantial subset of patients show autoimmune responses to one of the guardians of the immune system, interleukin-10 (IL-10), which leads to uncontrolled inflammation; and second, that this damaging immune response is the mechanism for one of the strongest known genetic risk factors for IBD.

Antibodies that block interleukin-10 (IL-10), a cell-to-cell messenger that normally acts as one of the body’s key controls on inflammation, effectively remove the immune system’s natural ‘brake’ on inflammation, allowing inflammatory responses to continue unchecked.

IBD, which includes Crohn’s disease and ulcerative colitis, affects ~500,000 people in the UK and millions worldwide. It is a lifelong condition that commonly begins in adolescence or early adulthood and can require repeated hospital treatment, long-term immunosuppressive medication and, in some cases, surgery. Despite advances in treatment, many patients cycle through multiple therapies without achieving lasting disease control – impacting their lives and costing the health care system millions.

The researchers found high levels of anti-IL10 neutralizing autoantibodies in the blood of ~3.5% of IBD patients, both Crohn’s disease and ulcerative colitis, but not in healthy individuals. This could equate to 15,000-20,000 people with IBD in the UK carrying these autoantibodies.

The researchers also found that the presence of these antibodies was strongly linked to carriage of a particular genetic variant known as HLA-DRB1*01:03.

The link between HLA-DRB1*01:03 and a severe form of inflammatory bowel disease was first identified by Oxford researchers 30 years ago. The new findings show that people carrying this variant are far more likely to develop antibodies that block IL-10, helping explain how the gene contributes to disease.

Professor Holm Uhlig, a Paediatric Gastroenterologist and Director of the Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, and a senior author of the study, 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.”

Sophie Hambleton, Professor of Paediatrics and Immunology at Newcastle University, 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.”

The researchers say the findings support the development of a blood test to identify this subgroup of patients, helping clinicians move quickly towards more appropriate treatment.

Dr Rainer Doffinger, Clinical immunologist at the 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 Kennedy Institute of Rheumatology, said: “This is 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.”

The findings represent an important step towards more personalised approaches to diagnosing and treating inflammatory bowel disease, where treatment can be guided by the underlying biology of a patient’s disease rather than symptoms alone.

The research was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre’s in Oxford, Cambridge and Newcastle.

Paper: Gharahdaghi N et al. IL-10 Autoantibodies and HLA-DRB101:03 in Inflammatory Bowel Disease. New England Journal of Medicine (2026).

Ends

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Notes to Editors

About inflammatory bowel disease (IBD)

• Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, affects around 1 in 123 people in the UK (more than 500,000 people).
  https://www.crohnsandcolitis.org.uk/about-crohns-and-colitis/what-is-crohns-and-colitis
• IBD often begins in adolescence or early adulthood and can have a substantial impact on quality of life, including pain, fatigue and unpredictable flare-ups.
  https://www.crohnsandcolitis.org.uk/about-crohns-and-colitis/symptoms

https://www.cicra.org/what-is-ibd/

• Some patients require surgery: around 1 in 5 people with Crohn’s disease and around 7% of those with ulcerative colitis require major surgery within five years of diagnosis.
  https://www.crohnsandcolitis.org.uk/about-crohns-and-colitis/treatments/surgery
• The global prevalence of IBD is rising, with some countries expected to exceed 1% of the population affected in coming decades.
  https://www.nature.com/articles/s41575-025-01097-1

About the study

• The study was possible through research in the Oxford-based Inflammatory Bowel disease cohort study at the Translational Gastroenterology & Liver Unit and the UK IBD BioResource study. The Inflammatory Bowel Disease (IBD) BioResource is a national platform that supports research into Crohn's disease and ulcerative colitis to increase understanding of IBD, accelerate the development of new and improving therapies and improve the care of patients. The aim is to recruit 55,000 patients with Crohn’s or ulcerative colitis, including 2,000 people newly diagnosed IBD. The paediatric arm of the IBD BioResource aims to build a cohort of at least 800 paediatric IBD patients. The IBD Bioressource will undertake research into genetics and biomarkers to understand the causes of Crohn’s disease and ulcerative colitis and identify genetic determinants of IBD severity and treatment response.  https://bioresource.nihr.ac.uk/programmes/ibd-bioresource

• The research was supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centres of Oxford, Cambridge and Newcastle.  The research involved several IBD cohorts and control individuals, including collaboration with Birmingham University and Aalborg Hospital in Denmark and was funded in part by the Wellcome Trust, by The Leona M. and Harry B. Helmsley Charitable Trust, the Medical Research Council and the Crohn’s in Childhood Research Association (CICRA).

About the Centre for Human Genetics

The Centre for Human Genetics (CHG) within the Nuffield Department of Medicine at University of Oxford is a leading research centre focused on understanding the genetic and molecular basis of human disease. Bringing together scientists, clinicians and public health researchers, the Centre conducts world-class research spanning genomics, infectious diseases, cancer, cardiovascular disease and rare disorders. CHG plays a critical role in the Nuffield Department of Medicine in translating scientific discoveries into improvements in healthcare and global health.

About the Nuffield Department of Medicine

NDM brings together more than 3,500 researchers, students and professional services staff across Oxford and international research programmes and partnerships in Africa, Asia and beyond. The department combines world-leading scientific expertise with advanced laboratories, clinical research facilities and cutting-edge technologies to tackle some of the world's most pressing health challenges.

Research across NDM spans infectious and tropical diseases, pandemics and vaccines, cancer, rare disease, immunology, genomics, translational medicine and global health. The Translational Gastroenterology & Liver Unit is part of NDM, specialising in immune-mediated inflammatory disease such as IBD. By translating discoveries from the laboratory into clinical practice, NDM helps improve patient care and informs national and global health policies. Through long-term partnerships and investment in local research leadership, training and infrastructure, the Department is committed to strengthening research capacity and advancing health equity around the world. https://www.ndm.ox.ac.uk/ .