The causes of inflammatory bowel disease (IBD) have been poorly understood, but now, scientists have pointed to a dysregulated immune response that may cause the condition in some patients.
ibdWhich is characterized by chronic inflammation of all or part of the digestive tract, affecting millions of people worldwide. Its major forms are Crohn’s disease, which can occur at any point in the gastrointestinal tract, and ulcerative colitis, which affects only the colon and rectum.
While IBD patients may experience similar inflammation, the underlying causes may differ. The researchers concluded in the new study that understanding those differences could potentially open up new, targeted angles for treatment.
“Early identification of these patients may ultimately allow physicians to move faster toward treatments that address specific mechanisms of disease rather than relying on a trial-and-error sequence of medications.” Dr. Brad Pasternakthe medical director of the IBD Clinic at Phoenix Children’s Hospital, who was not involved in the work, told Live Science in an email.
A possible subtype of IBD
The genetics of IBD are complex, with previous studies linking the condition to 300 “hotspots” throughout the genome.. The strongest known genetic risk factor for ulcerative colitis is a gene variant called HLA-DRB1*01:03, but how this variant contributes to IBD is unclear.
The new study, published June 10 The New England Journal of MedicineHelps connect the dots.
A big clue was revealed in Previous research was conducted by the same teamWho tested the blood of two children with IBD. The children had autoantibodies – immune proteins that target the body itself rather than germs – that were neutralizing a key anti-inflammatory protein called interleukin-10 (IL-10).
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Pasternak said IL-10 normally works by preventing the secretion of pro-inflammatory proteins, so patients whose bodies block IL-10 are effectively releasing a brake that is supposed to stop inflammation.
Researchers suspect that these autoantibodies may be one of the factors that cause IBD. In their latest study, they tried to find out whether more IBD patients had similar autoantibodies.
The study included data from more than 4,900 people with IBD and more than 1,000 people without the condition. Using two different lab tests, researchers analyzed blood samples from both groups, finding autoantibodies in 173 IBD patients, or about 3.5%. The autoantibody was virtually absent from the blood of the comparison group.
Then, in laboratory experiments, the team exposed immune cells in the blood of IBD patients to those carrying autoantibodies. This reduced the amount of IL-10, triggering a pro-inflammatory response.
Study co-authors Dr. Holm UhligIdentifying what triggers the formation of autoantibodies will be “a question of intense interest,” the pediatric gastroenterologist at the University of Oxford told Live Science. However, for now, their data suggest that patients with HLA-DRB1*01:03 are much more likely to have autoantibodies that block IL-10 than patients without the variant.
Historically, this type has been associated with severe IBD that may require major surgery to treat. “Currently, autoimmune reactions are not part of the therapeutic repertoire, and that’s why we think this is a relevant study,” Uhlig said.
Uhlig also noted that given the large number of IBD patients worldwide, the subgroup of 3.5% of patients they identified is a “significant number.”
In general, Pasternak said, many IBD patients are currently treated with therapies that broadly suppress inflammatory pathways, but not everyone responds to treatment. The study points to a possible way to someday tailor treatments to specific patients based on the mechanisms driving their diseases, he said.
In addition to offering personalized treatments for IBD patients, Uhlig said their findings could improve diagnosis.
“Patients may undergo genetic testing early in the diagnosis of their disease,” he said, “and this will then determine their susceptibility to developing autoantibodies.”
This article is for informational purposes only and is not intended to provide medical advice.
Gharahdaghi, N., Yeh, P., Ceron-Gutierrez, L., Griffin, H., Gordon, H., Jaymane, C., Fracchia, A., Chong, AY, Walsh, A., Brain, O., Baker, K., Kockelberg, H., Luo, Y., Becerra, MG, Vadakethala, K., Coy, M., Kabiri, L., Bernardo, M., Dunachie, S., . . . Uhlig, HH (2026). Interleukin-10 autoantibody and HLA-DRB1*01:03 in inflammatory bowel disease. New England Journal of Medicine, 394(22), 2212-2222. https://doi.org/10.1056/nejmoa2513654