Scientists Solve a 30-Year Mystery Behind Inflammatory Bowel Disease

Researchers from the UK and Denmark have solved a 30-year-old mystery by explaining how the HLA-DRB1*01:03 gene variant contributes to inflammatory bowel disease (IBD). The variant causes the immune system to produce antibodies that mistakenly target interleukin 10 (IL-10), a protein that normally regulates inflammation. Without IL-10’s protective effect, inflammation in the gut worsens, linking the genetic variant to severe IBD cases. The study analyzed blood samples from 4,900 people with IBD and 1,000 without, detecting IL-10-neutralizing antibodies in 3.5% of IBD patients but none in healthy controls. Among IBD subtypes, 2.5% of Crohn’s disease patients and 4.4% of ulcerative colitis patients had these antibodies, suggesting a significant subset of cases may be driven by this autoimmune response. The team also confirmed that HLA-DRB1*01:03 is strongly linked to the presence of these antibodies. Pediatric gastroenterologist Holm Uhlig from the University of Oxford called the findings the ‘missing link’ between the genetic variant and autoimmunity to IL-10, which had been suspected for decades. Clinical gastroenterologist Simon Travis described it as the most exciting discovery of his career, as it could lead to better disease management for affected patients. IBD affects millions worldwide, with rising case numbers. While the antibodies were found in only a small percentage of patients, the discovery could still impact treatment strategies for a significant number of people globally. Researchers now aim to explore targeted therapies that could neutralize these harmful antibodies, potentially improving outcomes for those with severe IBD.