An international study has uncovered insights into a rare immune mechanism that may help explain why some children develop particularly severe Inflammatory Bowel Disease (IBD).
The study, published in Gut, was led by researchers at the University of Oxford supported by the NIHR Biomedical Research Centres in Oxford, Cambridge and Newcastle, and involved young participants from the NIHR Paediatric Inflammatory Bowel Disease (PIBD) BioResource, which is led by Professor Holm Uhlig, the BRC Oxford’s Co-theme Lead for Inflammation across Tissues and senior author of the study.
The research, which also involved Boston Children’s Hospital, SickKids Toronto, the University of Southampton, Wellcome Sanger Institute and the University of Cambridge, built on a series of recent discoveries linking severe IBD to both a genetic marker known as HLA-DRB1*01:03 and neutralising autoantibodies against interleukin-10 (anti-IL-10). Interleukin-10 is an anti-inflammatory protein that controls intestinal immunity.
The study analysed samples from 1,045 children and young people with IBD from the UK, United States, Canada and Israel. The 330 UK participants were enrolled through the PIBD BioResource.
Earlier research had identified anti-IL-10 autoantibodies in two children with IBD. A subsequent study involving more than 3,300 IBD BioResource participants found the antibodies in a small proportion of people with IBD and revealed a strong link with the genetic variant HLA-DRB1*01:03. Another large genetic study involving more than 43,000 people with IBD showed that HLA-DRB101:03 is associated with more severe forms of Crohn’s disease and ulcerative colitis.
IBD is a lifelong condition that causes inflammation in the digestive system. The two main forms of IBD, Crohn’s disease and ulcerative colitis, can cause abdominal pain, diarrhoea, fatigue and weight loss.
While IBD can develop at any age, increasing numbers of children and young people are being diagnosed with the condition. Paediatric IBD is often more aggressive than adult-onset disease and can affect growth, development and quality of life.
In this new study, researchers found anti-IL-10 autoantibodies in 26 children, representing around 2.5% of those tested. They showed that these autoantibodies block the activity of interleukin-10, a protein that normally helps control inflammation in the gut. When IL-10 was blocked, inflammatory immune responses increased, suggesting that the autoantibodies may exacerbate inflammation in this group of patients.
The researchers also confirmed the link between anti-IL-10 and HLA-DRB1*01:03. Among children with available genetic data, 80% of those who tested positive for anti-IL-10 carried the genetic variant.
Importantly, children with anti-IL-10 autoantibodies appeared to have a more severe disease course. They were more likely to have difficult-to-treat IBD, experience acute severe ulcerative colitis and require a colectomy – an operation to remove all or part of your colon (large intestine). Children with anti-IL-10 autoantibodies had an average age of 13 years when diagnosed with IBD.
While further research is needed, the findings suggest that testing for anti-IL-10 autoantibodies could one day help identify children at risk of severe disease and inform treatment decisions. The study also opens up new opportunities to investigate therapies that target the production of these autoantibodies. Together, the findings provide a clearer picture of a small but important subgroup of children living with IBD.