New Gene Variants Discovered in IBD, More Precise Treatment to Follow


Genetic variants regulate immune cells with important roles in immunodeficiency disorders.

Genetic variants regulate immune cells with important roles in immunodeficiency disorders.

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may soon access more personalized, precise treatments thanks to a discovery of new gene variants associated with the disease that affects children under 5 years of age.

“As we continue to understand the specific functions of these genes in this type of childhood-onset disease, we are working to design more effective therapies,” said study leader Judith R. Kelsen, MD, a pediatric gastroenterologist in the Center for Pediatric Inflammatory Bowel Disease at The Children’s Hospital of Philadelphia (CHOP).

IBD beginning in childhood is oftentimes more severe than adult-onset IBD, and VEO-IBD is more severe than IBD that appears in later childhood years.

“There has been extensive research in the genes contributing to adult-onset IBD and in children aged 10 and older, but relatively little research has been performed in the very early-onset subtype of the disease,” Dr. Kelsen said.

Previous research in the area dealt mainly with genome-wide association studied (GWAS), which do not have the capacity to detect rare gene variants. The current study used whole exome sequencing, which has revolutionized the ability to study rare gene variants.

The researchers evaluated 125 patients with VEO-IBD who were under the age of 4 years, along with 19 of their parents’ DNA. A control group of 210 patients included 145 healthy individuals, 45 patients with pediatric IBD, and 20 with adult-onset Crohn’s disease.

To compensate for the fact that IBD is very complex and can lead to a patient’s genes altering immune response to environmental exposure, researchers focused on specific genes or biological pathways associated with primary immunodeficiency disorders.

The researchers found new, rare variants in genes that regulate B-cells and T-cells, immune cells with important roles in immunodeficiency disorders. In a key immune function pathway, scientists discovered rare variants in the IL10RA gene.

“Our findings reinforce other research that has revealed considerable overlap among genes involved in different immune-related diseases,” Dr. Kelsen said. “This overlap is reflected in the fact that VEO-IBD may be a form of primary immunodeficiency.”

For physicians treating patients with IBD, Kelsen said the research underlines the importance of doing complete immunological workups for these patients, in addition to IBD evaluations.

“Sometimes a genetic workup may also be necessary,” she noted. “Evaluation and treatment guidelines are not yet standardized for children with VEO-IBD, but we have found that this subtype of IBD is somewhat different from IBD that begins later. As we better understand the specific components of the immune system that may be involved in this disease, clinicians will be better prepared to individualize treatment to each patient.”

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