Inflamm Bowel Dis. 2020 Aug 14;izaa209. doi: 10.1093/ibd/izaa209. Online ahead of print.

Suruchi K Batra ¹, Christopher R Heier ^2 3, Lina Diaz-Calderon ¹, Christopher B Tully ², Alyson A Fiorillo ^2 3, John van den Anker ⁴, Laurie S Conklin ¹

Author information

• ¹Division of Gastroenterology, Hepatology and Nutrition, Children's National Hospital, Washington, DC, USA.
• ²Research Center for Genetic Medicine, Children's National Hospital, Washington, DC, USA.
• ³Department of Genomics and Precision Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• ⁴Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.

Abstract

Background: We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers.

Methods: Clinical response was assessed by Pediatric Crohn's Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (n = 11) and nonresponders (n = 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls.

Results: Discovery cohort analysis identified 7 miRNAs associated with therapeutic response: 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls.

Conclusions: Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.