Inflammatory bowel disease (IBD) affects around half a million people in the UK, yet despite decades of research, scientists have still not fully understood why it develops.
Now, our researchers have helped uncover an important biological driver of severe IBD – a discovery that could pave the way for preemptive testing and targeted treatment of these individuals.
The findings, published in the New England Journal of Medicine, Gut and The Lancet Gastroenterology and Hepatology reveal how the body's own immune system can switch off one of its most important anti-inflammatory signals, leading to uncontrolled inflammation in the gut.
Contents:
- What is inflammatory bowel disease?
- Looking beyond symptoms to understand the biology
- A missing piece of the puzzle
- Moving towards personalised treatment for IBD
What is inflammatory bowel disease?
Inflammatory bowel disease (IBD) is the name given to a group of lifelong conditions involving chronic inflammation of the digestive tract. The two main forms are Crohn's disease and ulcerative colitis.
People with IBD experience periods when symptoms flare up, followed by times when the disease is less active. Symptoms can include abdominal pain, diarrhoea, fatigue, weight loss, and rectal bleeding. Living with IBD often means managing unpredictable flare-ups that can affect work, education, relationships, and everyday life.
The condition most commonly begins during adolescence or early adulthood and, while treatments have improved considerably, many patients still cycle through multiple medications without achieving long-term disease control. Some require repeated hospital admissions or surgery, highlighting the need for a better understanding of the different biological processes that drive the disease.
Looking beyond symptoms to understand the biology
Although Crohn's disease and ulcerative colitis are often discussed as single conditions, researchers increasingly recognise that IBD is made up of several biologically distinct diseases. Understanding those differences is a key step towards precision medicine – identifying the right treatment for the right patient based on the biology driving their disease, rather than relying solely on symptoms.
Researchers from Newcastle University’s Translational and Clinical Research Institute, alongside colleagues from the Universities of Oxford and Cambridge, and with support from the NIHR Biomedical Research Centres in all three cities, have now identified a new mechanism driving inflammation in around one in thirty IBD sufferers.
A missing piece of the puzzle
The research team built on their earlier finding in two young children with IBD, who turned out to have neutralised one of the body’s ‘guardians of the immune system’, known as interleukin-10 (IL-10). This molecule normally acts as one of the body's natural brakes on inflammation.
Genetic spelling mistakes in IL-10 or its receptor were already known to cause childhood IBD. This research implied that blocking antibodies formed by the body’s own immune system against IL-10 mimicked this effect, allowing inflammation in the gut to continue unchecked.
Following up those early observations required collaboration across multiple research centres and the participation of thousands of patients.
The team investigated whether antibodies against IL-10 might explain IBD in the wider population. They analysed samples from more than 5,000 people with IBD and made two major discoveries. They found that around 3.5% of adult IBD patients showed blocking antibodies against IL-10, while the proportion in children with IBD was around 2.2%. This response was not found in the blood of healthy patients, but only in patients with IBD, whether Crohn’s disease or ulcerative colitis.
This could equate to 15,000–20,000 people with IBD in the UK carrying these autoantibodies.
The researchers also discovered that these antibodies are strongly linked to a genetic variant known as HLA-DRB101:03, helping to explain one of the strongest known inherited risk factors for IBD, especially severe IBD.
It had long been a mystery how HLA-DRB1*01:03 drove inflammation in the gut. We can now recognise that it does so via an increased tendency to make autoantibodies to IL-10. It is the antibodies that confer the significantly higher risk of severe IBD, requiring advanced medical and surgical therapies.
Together, these findings provide a biological explanation for disease in a distinct group of IBD patients and reinforce the idea that IBD should be understood as a collection of related disorders, rather than a single disease.
Moving towards personalised treatment for IBD
Understanding what drives the inflammation provides a clear explanation for disease in this group of people and potentially opens the door to new treatments that target the autoantibodies themselves or cells that produce those autoantibodies. Clinical trials are planned to explore these possibilities in a systematic way.
A simple blood test could be developed to identify the sub-group of patients carrying the autoantibodies so that they could benefit from this personalised medicine.
This research also highlights the value of studying rare diseases. By understanding the biology of uncommon inherited disorders, researchers can uncover fundamental mechanisms that improve the diagnosis and treatment of much more common conditions.
You might also like
- read the press release: Scientists uncover key cause of inflammatory bowel disease
- explore how Newcastle University’s Translational and Clinical Research Institute are transforming research into life-changing treatments and improving patient outcomes every day
- read the research articles:
- ‘IL-10 Autoantibodies and HLA-DRB101:03 in Inflammatory Bowel Disease’. Nima Gharahdaghi et al. (2026) New England Journal of Medicine. DOI:10.1056/NEJMoa2513654
- “Neutralising autoantibodies against IL-10 and HLA-DRB1*01:03 in paediatric patients with inflammatory bowel disease”. Nima Gharahdaghi et al. (2026) Gut. DOI:10.1136/gutjnl-2026-339329
- “Neutralizing Autoantibodies against Interleukin-10 in Inflammatory Bowel Disease”. Helen Griffin et al. (2024) New England Journal of Medicine. DOI:10.1056/nejmoa2312302
- discover the work of Dr Sophie Hambleton, Professor of Paediatrics and Immunology in our Faculty of Medical Sciences
- discover the work of Professor Holm Uhlig, Paediatric Gastroenterologist and Director of the Centre for Human Genetics at the University of Oxford
