Study identifies new disease-inducing mechanism for inflammatory bowel disease

Combined, Crohn’s disease and ulcerative colitis affect over 500,000 people in the UK

Researchers from Newcastle University, Great North Children’s Hospital, Cambridge University Hospital and the universities of Cambridge and Oxford have identified a new disease-inducing mechanism for inflammatory bowel disease (IBD).

The study published in the New England Journal of Medicine found that self-directed antibodies attacked interleukin-10 (IL10), an anti-inflammatory protein that controls intestinal immunity, in two patients with early-onset severe IBD.

Collectively known as IBD, Crohn’s disease and ulcerative colitis are incurable conditions that involve excessive inflammation in the gut and affect over 500,000 people in the UK, according to Crohn’s & Colitis UK.

Supported by the National Institute for Health and Care Research (NIHR), Cambridge Biomedical Research Centre, NIHR Oxford BRC and the Leona M. and Harry B. Helmsley Charitable Trust, and part-funded by the Wellcome Trust, scientists discovered that these antibodies prevented IL10 from binding to its receptor, ultimately causing an increased inflammatory response in patients.

The team found that children with genetic defects in IL10, or its receptors, suffer from a severe form of IBD that typically presents within the first few months of life.

As a result, the team treated one patient with precision medicine that suppressed antibody production, which led to the disappearance of the anti-IL10 autoantibodies as well as the resolution of IBD.

Rainer Döffinger, consultant clinical scientist of the department of clinical biochemistry and immunology at Cambridge University Hospitals, said: “This discovery adds to a growing body of evidence showing the severe consequences when the body’s immune defence is attacking itself.

“The study is the result of cutting-edge NHS diagnostics and an… efficient collaboration between the centres to deliver results with real-world implications for new therapies that will ease the burden of suffering [for] patients with IBD.”

Researchers hope that these findings could have a wider implication for patients beyond infancy.