Scientists Solve 30-Year Mystery Behind Inflammatory Bowel Disease, Identify Hidden Immune Trigger

Scientists have identified a previously unexplained immune system abnormality that may be responsible for inflammatory bowel disease in a small group of patients. A new study suggests that certain antibodies block a protein responsible for controlling inflammation, potentially opening the way for more targeted treatments.

Published in the New England Journal of Medicine, the study conducted by researchers at the University of Oxford, Newcastle University and Cambridge University Hospitals NHS Foundation Trust investigated the immune mechanisms underlying inflammatory bowel disease (IBD).

IBD includes Crohn's disease and ulcerative colitis, chronic conditions characterised by intestinal inflammation, abdominal pain, diarrhoea and other digestive complications.

Researchers examined more than 4,900 people with IBD and identified antibodies that interfere with interleukin-10 (IL-10), an important protein that helps regulate immune responses and prevent excessive inflammation.

The findings revealed that approximately 3.5% of patients with IBD had elevated levels of antibodies capable of neutralising IL-10.

These antibodies were detected in patients with both Crohn's disease and ulcerative colitis but were not identified in healthy individuals.

Researchers explained that blocking IL-10 disrupts the immune system's ability to control inflammation, allowing persistent inflammatory activity in the intestines.

Importantly, the study also identified a strong connection between these antibodies and a genetic variant known as HLA-DRB1*01:03.

This genetic variant had been associated with severe IBD for approximately 30 years, but its underlying disease mechanism remained unclear.

The findings suggest that individuals carrying this variant may be more likely to develop IL-10-blocking antibodies, providing a possible explanation for their increased disease susceptibility.

Researchers believe these antibodies could eventually serve as biomarkers to identify patients who may benefit from specialised treatment.

Potential therapies could target the antibodies themselves or the immune cells responsible for producing them.

However, further research is needed to establish the safety and effectiveness of such approaches.

REFERENCE: Nima Gharahdaghi, et al.; Interleukin-10 Autoantibodies and HLA-DRB1*01:03 in Inflammatory Bowel Disease. New England Journal of Medicine, 2026; 394 (22): 2212 DOI: 10.1056/NEJMoa2513654