Scientists from the University of Oxford, Newcastle University and Cambridge University Hospitals NHS Foundation Trust have uncovered an important driver of inflammatory bowel disease, helping to solve a decades-old puzzle in the genetics of the condition.
The study, published in the New England Journal of Medicine, identifies a damaging immune response against interleukin-10 (IL-10), a key molecule that normally helps control inflammation. The researchers found that, in a subset of people with inflammatory bowel disease, autoantibodies block IL-10, effectively removing one of the immune system’s natural “brakes” on inflammation.
The work also explains the mechanism behind one of the strongest known genetic risk factors for severe inflammatory bowel disease: HLA-DRB1*01:03. This genetic association was first identified by Oxford researchers 30 years ago, but until now it was not clear how it contributed to disease.
Professor Holm Uhlig, Director of the Centre for Human Genetics and senior author on the study, worked alongside collaborators including Professor Sophie Hambleton at Newcastle University, Dr Rainer Doffinger at Cambridge University Hospitals NHS Foundation Trust, and Professor Simon Travis at the University of Oxford and the Kennedy Institute of Rheumatology.
Professor Uhlig 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."
Interleukin 10 (IL-10) cytokine protein
Inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis, affects around 500,000 people in the UK and millions worldwide. The researchers found high levels of anti-IL-10 neutralising autoantibodies in around 3.5% of patients with inflammatory bowel disease, suggesting that thousands of people in the UK could belong to this biologically distinct subgroup.
The findings support the development of a blood test to identify patients with this form of disease, helping clinicians move towards more personalised and targeted treatment. They also reinforce the idea that inflammatory bowel disease is not a single condition, but a group of diseases driven by different underlying biological mechanisms.
This discovery represents an important step towards understanding inflammatory bowel disease according to its underlying cause, rather than symptoms alone, and could help guide future diagnostic and treatment strategies.
The research was supported by the National Institute for Health and Care Research Biomedical Research Centres in Oxford, Cambridge and Newcastle.
The paper, 'IL-10 Autoantibodies and HLA-DRB101:03 in Inflammatory Bowel Disease', is published in the New England Journal of Medicine.
Read the full story on the Nuffield Department of Medicine website.