A study led by researchers at the Children’s Hospital of Philadelphia (CHOP) revealed specific genetic variants carried by children with very early onset of inflammatory bowel disease (IBD). The study is entitled “Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients With Very Early Onset Inflammatory Bowel Disease” and was published in the journal Gastroenterology.

IBD is a chronic inflammatory condition of the gastrointestinal tract that primarily comprises ulcerative colitis and Crohn’s disease. It is characterized by vomiting, abdominal pain, rectal bleeding, diarrhea, internal cramps in the pelvis region, fatigue and weight loss. It is estimated that IBD affects approximately two million children and adults in the United States.

Very early onset cases of IBD (in children aged 5 years or younger) are usually characterized by a more severe phenotype than IBD cases at an older age onset. In the study, researchers assessed whether very early onset IBD patients had rare or new variants in genes known to be associated with primary immunodeficiency disorders and related pathways, which could, therefore, contribute to disease development.

“There has been extensive research in the genes contributing to adult-onset IBD and in children aged 10 and older,” noted the study’s lead author and pediatric gastroenterologist at CHOP, Dr. Judith R. Kelsen in a news release, “but relatively little research has been performed in the very-early onset subtype of the disease.”

The team analyzed the DNA of 125 patients with very early onset IBD (from 3 weeks of age to 4 years old) and of 19 parents (4 with IBD). As controls, data from 45 pediatric IBD patients, 20 adult-onset Crohn’s disease patients and 145 healthy individuals were also analyzed. The team employed a recent new technology – whole exome sequencing – which has revolutionized the ability to study rare genetic variants.

Researchers found rare and novel variants that potentially contribute to the development of very early onset IBD. Interestingly, the variants were found in genes known to be involved in the regulation of important cells of the immune system – B and T cells, and to play important roles in immunodeficiency disorders, namely rare variants in the IL10RA gene and previously unidentified variants in the MSH5 and CD19 genes.

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

The research team concluded that patients with very early onset IBD carry variants in specific genes that regulate important immune functions. The authors believe that these genetic variants contribute to IBD pathogenesis in younger children, and that they may allow the development of more precise and personalized treatments.

“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,” concluded Dr. Kelsen. “Evaluation and treatment guidelines are not yet standardized for children with very early-onset 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.”