Potential Marker Can Personalize Treatment in Crohn Disease

MicroRNA-31 (miR-31)—a single RNA gene—may help predict which subtype of Crohn disease (CD) a patient has, according to results from a new study.

The use of miR-31 as a marker can separate individuals with CD into subtypes in order to determine which therapeutics work best for each subtype and to better predict CD behavior.

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“These findings represent significant progress in molecularly defining the CDs, moving closer toward potential personalization of therapy and improving outcomes,” the researchers wrote.

CD is highly heterogeneous, which has impacted the ability to investigate new therapies among groups of patients with CD in clinical trials.

For this study, the researchers isolated colonic epithelial cells and immune cells from colonic tissues to measure miR-31 expression. To determine disease outcomes, small RNA-sequencing of formalin-fixed paraffin-embedded colon and ileum biopsies were performed among treatment-naïve pediatric patients with CD and controls.

Results showed 2 distinct molecular subtypes with different clinical associations, with the miR-31 expression as the driver.

Among adult patients, low colonic miR-31 expression levels at the time of surgery were associated with worse outcomes, including need for an end ileostomy and recurrence of disease in the neoterminal ileum.

Among pediatric patients, low miR-31 expression at diagnosis was associated with future development of fibrostenotic ileal CD that would require surgery.

“We have provided the most comprehensive molecular characterization of CD to date, to our knowledge,” the researchers wrote. “We have uncovered miR-31 as an identifier of CD but, more importantly, as a molecular stratifier of both pediatric and adult patients, an indicator of established disease phenotype in adult patients, and a predictor of clinical phenotype at the time of diagnosis in pediatric patients.”

Future research will decipher the role miR-31 has in the integrity of the gut epithelium.

—Colleen Murphy

Reference:

Keith BP, Barrow JB, Toyonaga T, et al. Colonic epithelial miR-31 associates with the development of Crohn’s phenotypes [published online October 4, 2018]. JCI Insight. https://doi.org/10.1172/jci.insight.122788.