Antibodies found in 3.5% of patients
The researchers tested about 4,900 people with inflammatory bowel disease (IBD) and about 1,000 healthy controls for antibodies that neutralize interleukin-10, or IL-10. They detected these antibodies in 3.5% of patients, but in none of the controls. Oxford researchers estimate that this prevalence could correspond to 15,000 to 20,000 people with IBD in the UK.
IBD includes Crohn's disease and ulcerative colitis and affects around 500,000 people in the UK and millions worldwide, according to Oxford's Nuffield Department of Medicine. The conditions cause recurring or persistent inflammation in the digestive tract, often beginning early in life. Some patients experience lifelong symptoms and complications despite medication, surgery or dietary changes.
The study brought together Oxford's Nuffield Department of Medicine, Newcastle University and Cambridge University Hospitals NHS Foundation Trust. Support came from the National Institute for Health and Care Research Biomedical Research Centres in Oxford, Cambridge and Newcastle.
How blocking IL-10 could intensify inflammation
IL-10 helps prevent excessive immune responses in the gut by restraining inflammation-promoting cells and reducing their production of other inflammatory substances. Antibodies that neutralize it could weaken that protection, allowing intestinal inflammation to become more intense.
Researchers already knew that genetic defects in the IL-10 signaling pathway could cause severe intestinal inflammation, often in infancy. Earlier studies had also identified IL-10-neutralizing antibodies in children with early-onset disease. The new work examined whether these antibodies were present in a broader group of patients.
Laboratory findings supported their ability to interfere with IL-10. Serum with high anti-IL-10 activity had less detectable IL-10 and a stronger proinflammatory cytokine response. In a laboratory cytokine-release assay, levels of IL-23, IL-1β, TNF and IL-6 increased, consistent with the antibodies functionally blocking IL-10 signaling.
A commentary in Signal Transduction and Targeted Therapy detailed differences across the study groups: anti-IL-10 IgG positivity was 5.3% in the Oxford IBD Discovery cohort, 3.1% in the Oxford IBD Validation cohort and 3.2% in the U.K. IBD BioResource cohort. By diagnosis, neutralizing antibodies were detected in 2.5% of patients with Crohn's disease, 4.4% with ulcerative colitis and 5.9% with unclassified IBD.
The antibodies also persisted in some patients. Among 10 people followed for periods ranging from 0.3 to 14 years, seven, or 70%, showed long-term persistence of neutralizing anti-IL-10 IgG.
A possible explanation for a genetic risk
The antibody findings may help explain the role of HLA-DRB1*01:03, a gene variant associated with certain forms of intestinal inflammation for about 30 years. The New England Journal of Medicine study describes it as the strongest genetic risk factor for ulcerative colitis.
The affected gene encodes part of immune proteins that display fragments of foreign substances on cell surfaces for recognition by immune cells. How this particular variant influences IBD risk had remained unclear.
People carrying HLA-DRB1*01:03 were much more likely to test positive for anti-IL-10 antibodies. Using imputed genetic data, the researchers reported an odds ratio of 50.0 in the Oxford cohort, with a 95% confidence interval of 16.4 to 152.3. The corresponding figure in the U.K. IBD BioResource cohort was 24.7, with a confidence interval of 14.5 to 42.1. A high-resolution sequencing analysis of the Oxford cohort yielded an odds ratio of 29.5, with a confidence interval of 12.2 to 71.1.
The association offers a possible mechanism connecting the variant to IBD: carriers are more likely to have antibodies that interfere with an important control on inflammation. The researchers present this as a possible explanation, not an established cause of IBD in all patients.
A separate study in children
A multicenter study published online in Gut on August 11, 2026, identified anti-IL-10 autoantibodies in 26 of 1,045 pediatric IBD patients, or 2.5%, across cohorts from four countries.
Compared with matched controls, antibody-positive children had more severe disease. Difficult-to-treat disease occurred in 23% versus 6%, acute severe ulcerative colitis in 26% versus 6%, and colectomy in 27% versus 6%. HLA data were available for 20 antibody-positive patients; 16 of them, or 80%, carried HLA-DRB1*01:03.
Potential tests and targeted treatments
The Oxford findings suggest possible avenues for diagnosis and treatment. The team around Dr. Nima Gharahdaghi and Professor Holm Uhlig proposes that the antibodies could provide the basis for a blood test to identify IBD.
The Signal Transduction and Targeted Therapy commentary suggests that screening for both HLA-DRB1*01:03 and anti-IL-10 autoantibodies may help avoid ineffective treatment with standard anti-inflammatory or immunosuppressive drugs. It points to a need for therapies aimed at the B cells responsible for autoantibody production.
The commentary also describes individual treatment cases involving anti-IL-10-positive patients with refractory disease. One of the initially identified patients with infantile-onset IBD and neutralizing IL-10 antibodies was successfully treated with anti-CD20 therapy. In another patient with massive B-cell infiltration, CAR T-cell therapy depleted B cells and promoted clinical remission.
