We aimed to see if children have a greater genetic susceptibility for this type of inflammatory bowel disease because they develop it so young. Unlike other inflammatory bowel diseases, very early onset inflammatory bowel disease is diagnosed in patients before the age of 6, occurring in four out of every 100,000 births worldwide. In such young patients, the disease does not often respond to anti-inflammatory medications, and sometimes requires surgery to remove all or parts of the colon.

Inflammatory bowel diseases are chronic, inflammatory conditions—including Crohn's disease and ulcerative colitis—that occur when immune cells in the intestines are over-activated and cause sustained inflammation in the gut. These diseases are thought to be caused by multiple genetic mutations and environmental factors, such as diet and pollution as well as disruptions to the makeup of gut bacteria. Treatments usually include prescription drugs that curb inflammation.

The combined research teams found IFIH1 mutations in four of the 18 new patients, bringing the total of IFIH1 mutations found to 8 out of the 42 patients. Among the IFIH1 mutations, the researchers discovered nine mutations which resulted in abnormal production of a protein called MDA5. In the eight patients with the mutations, MDA5 function was much lower than normal.

When functioning properly, MDA5 is a part of the inborn immune system that helps fight off viruses in the gut. Using protein assays that mimicked the activity of normal and abnormal MDA5, the researchers found that in each patient with the IFIH1 mutation, the MDA5 proteins only partially worked, but not enough to do their job of battling viruses. The researchers suspect this loss of function in the protein causes the improper activation of the immune system, triggering the inflammation that leads to very early onset inflammatory bowel disease.

Regards

John
EditorialAssistant
Immunogenetics Open Access