Researchers discover major cause of IBD - Video

In a study published in the journal Nature, researchers have identified a significant cause of inflammatory bowel disease (IBD) and several other immune disorders affecting the spine, liver, and arteries, offering new hope for millions of people worldwide.

Nearly 5% of humans live with an autoimmune or inflammatory disease. They arise when the immune system attacks the bowel, causing an array of debilitating symptoms from abdominal pain and weight loss to diarrhoea and blood in stools. While medicines such as steroids can ease the symptoms, some patients require surgery to remove part of their bowel.

These heterogeneous conditions, ranging from Crohn’s disease and ulcerative colitis to psoriasis and lupus, all require better therapies, but only 10% of drugs entering clinical development ever become approved treatments. This high failure rate is mainly due to a lack of efficacy and reflects the poor understanding of disease mechanisms.

In the study, Dr. James Lee and his team made a key discovery while researching a "gene desert," a part of DNA on chromosome 21 that doesn't code for proteins but is linked to IBD and other autoimmune diseases. They found a section of DNA that acts like a volume control for nearby genes. This "enhancer" was only found in immune cells called macrophages and increased the activity of a gene ETS2, raising the risk of IBD. The researchers showed that ETS2 is important for the inflammatory behaviour of macrophages and their ability to damage the bowel in IBD. This same process is believed to cause other autoimmune disorders and some rare diseases affecting the liver and arteries.

“Crohn’s and colitis are complex, lifelong conditions for which there is no cure, but research like this is helping us to answer some of the big questions about what causes them. What we have found is one of the very central pathways that goes wrong when people get inflammatory bowel disease and this has been something of a holy grail. This research is a really exciting step towards the possibility of a world free from Crohn’s and colitis,” said Lee.

Reference: Stankey, C.T., Bourges, C., Haag, L.M. et al. A disease-associated gene desert directs macrophage inflammation through ETS2. Nature (2024). https://doi.org/10.1038/s41586-024-07501-1