For decades, inflammatory bowel disease (IBD) has been treated as a single disorder, even though patients often experience dramatically different symptoms, disease courses, and responses to therapy. A new study suggests there may be a good reason for that: what doctors call IBD could actually be a collection of distinct diseases driven by different biological mechanisms.

Researchers from the University of Oxford’s Nuffield Department of Medicine, Newcastle University’s Translational and Clinical Research Institute, and the Department of Immunology at Cambridge University Hospitals NHS Foundation Trust have identified a key driver of disease in a subset of patients. Their findings, published in the New England Journal of Medicine, reveal an immune malfunction that not only triggers uncontrolled inflammation but also helps explain one of the strongest genetic risk factors linked to IBD.

The team analyzed more than 4,900 people with Crohn’s disease and ulcerative colitis, the two main forms of IBD. They discovered that some patients develop autoimmune responses against interleukin-10 (IL-10), a crucial molecule that normally acts as one of the body’s primary brakes on inflammation. They also found that this immune attack is closely tied to a genetic variant long associated with severe IBD.

Under normal circumstances, IL-10 helps prevent the immune system from overreacting and damaging healthy tissue. But when antibodies block IL-10, this protective mechanism is disabled, allowing inflammation to persist unchecked and potentially fueling disease.