An international team of researchers has revealed the mechanism that explains why a genetic variant of the HLA-DRB1 gene is linked to a higher likelihood of developing severe Crohn's disease and ulcerative colitis.
The New England Journal of Medicine reported that an international team of researchers in the United Kingdom and Denmark has uncovered a biological mechanism that has remained a major mystery in inflammatory bowel diseases for more than three decades.
Inflammatory bowel disease (IBD) mainly includes Crohn's disease and ulcerative colitis, two chronic conditions that cause inflammation of the digestive tract, abdominal pain and digestive disorders, significantly affecting the quality of life of millions of people worldwide.
Scientists had observed years ago that the HLA-DRB1*01:03 gene variant was more prevalent among patients with severe forms of inflammatory bowel disease, but the underlying biological reason for this association remained unknown.
During the study, researchers analyzed blood samples from approximately 4,900 patients with inflammatory bowel disease, along with nearly 1,000 healthy volunteers. The results revealed the presence of antibodies that mimic the effects of interleukin-10 (IL-10) in about 3.5 percent of the patients, while these antibodies were not detected in any member of the control group.
The data showed that these antibodies were found in 2.5 percent of Crohn's disease patients and 4.4 percent of ulcerative colitis patients.
Further genetic analysis also revealed that the HLA-DRB1*01:03 variant is most strongly associated with the presence of these antibodies, providing a possible explanation for the relationship between this genetic variant and the risk of developing severe forms of the disease.
Dr. Simon Travis, a gastroenterologist at Oxford University, said: "This is one of the most exciting findings of my career in inflammatory bowel disease. We can now identify a group of patients whose direct cause of illness we know, which could open the door to a radical change in treatment methods."
For her part, Dr. Sophie Hambleton from Newcastle University confirmed that the study's findings highlight the importance of studying rare genetic disorders to understand the mechanisms underlying common diseases and to develop more precise treatment strategies.
