Genes Tied to Immune Response Differentially Expressed in Kids With Crohn's, UC

By Will Boggs MD

February 07, 2017

NEW YORK (Reuters Health) - The expression of genes related to mucosal immune responses differs between ulcerative colitis (UC) and colon-only Crohn's disease (CD) in pediatric patients, researchers report.

"At diagnosis, there are specific differences in mucosal cytokine response between children with ulcerative colitis and Crohn's colitis that may be useful for distinguishing these diseases and for predicting response to therapy," Dr. Michael J. Rosen from Cincinnati Children's Hospital Medical Center, in Ohio, told Reuters Health by email.

About 50% of children with inflammatory bowel disease (IBD) have isolated colitis, with many exhibiting overlapping or atypical features that hinder a specific diagnosis of Crohn's disease (CD) or ulcerative colitis (UC).

Dr. Rosen and colleagues investigated the rectal mucosal expression of genes associated with type 1, type 2, and type 17 inflammation in 56 children with UC, 36 with colon-only CD, 46 with ileocolonic CD, and 49 non-IBD controls.

UC patients were the only group to exhibit significantly increased rectal expression of the genes for the type 2 cytokines IL5 and IL13, the researchers report in Gastroenterology, online January 26.

Compared with colon-only-CD patients, UC patients had significantly increased rectal expression of genes associated with type 2 and type 17 (IL17A and IL23A) immune responses, a finding that was not explained by differences in overall inflammation as measured by S100A8 expression.

Increased expression of IL5 and IL17A genes best discriminated between UC and colon-only CD.

Higher expression of IL13 among UC patients was associated with increased likelihood of clinical response at six and 12 months and with a trend toward clinical remission at 12 months.

In contrast, there were no associations between IL13 expression and clinical outcome in CD patients.

"Since there are no therapies designed to specifically block type 2 (i.e., Th2) cytokines such as IL5 and IL13 for the treatment of ulcerative colitis, we thought that treatment-naive pediatric patients with a heightened expression of these cytokines in their rectal mucosal would respond poorly to traditional therapy," Dr. Rosen said. "Therefore, we were surprised to find that patients with a gene expression pattern marked by detectable expression of IL13 mRNA were 5 times more likely to achieve steroid-free clinical revision 12 months after diagnosis."

"Further validation of our results will be needed before they can be directly applied to clinical practice," he said. "That being said, our findings support that mucosal immune gene expression could be developed as a diagnostic tool for distinguishing ulcerative colitis from Crohn's disease in pediatric patients."

"We need studies of larger pediatric ulcerative colitis cohorts to determine whether gene expression associated with type 2 inflammation predicts response to specific therapies," Dr. Rosen added. "As more therapies for ulcerative colitis with different mechanisms of action become available, the ultimate goal will be to have an assessment of a patient's mucosal immune response that predicts which therapy will be the most effective for that patient."


Gastroenterology 2017.