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

by Lucy Pritchard, University of Oxford

edited by Stephanie Baum, reviewed by Robert Egan

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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 analyzed more than 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 about 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.

Key findings from the study

The researchers found high levels of anti-IL10 neutralizing autoantibodies in the blood of about 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 pediatric 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."

Experts on treatment potential

Sophie Hambleton, professor of pediatrics 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 realized that neutralizing autoantibodies against IL-10 was mimicking this effect in two 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 toward more appropriate treatment.

Dr. Rainer Doffinger, clinical immunologist at Cambridge University Hospitals NHS Foundation Trust, noted, "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, added, "This is the most exciting discovery in a lifetime specializing 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 toward more personalized 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.

Publication details

IL-10 Autoantibodies and HLA-DRB101:03 in Inflammatory Bowel Disease, New England Journal of Medicine (2026).

Journal information: New England Journal of Medicine

Key medical concepts

Inflammatory Bowel DiseasesInterleukin-10

Clinical categories

GastroenterologyAllergy and immunologyCommon illnesses & PreventionClinical genetics Provided by University of Oxford Who's behind this story?

Stephanie Baum

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