Understanding the impact of IL2RA polymorphism on clinical response

Summary

Inflammatory bowel diseases comprise mainly ulcerative colitis and Crohn's disease, and can cause disabling symptoms of abdominal pain, diarrhoea, and fatigue. The precise cause is unknown, but it appears that a triggering event in an individual with inherited genetic risk leads to long-lasting inflammation in the gut. Whilst many new treatments are being developed, around a third of patients do not have a good response to therapy, and gastroenterologists are not well-equipped to understand which treatment is most likely to work for each patient. Our research group has studied the effect of a known genetic mutation on the behaviour of immune cells in people with inflammatory bowel disease (IBD). The mutation is carried by about 1 in 6 patients in a European population, and is known to put patients at risk of developing IBD. We found that patients who carry the mutation have more activity in a process known as the 'Jak/Stat' pathway, and that some types of their immune cells can behave in a way that drives inflammation. The 'Jak/Stat' biological pathway is blocked by a new medication used in the treatment of IBD. We believe that patients who carry the genetic mutation are particularly likely to benefit from treatment  that inhibits this pathway, because of the extra activity seen in this biological pathway. We are requesting access to genetic and clinical data in order to see whether this effect is seen in groups of patients treated with 'Jak/Stat'-targeted therapy.