Abstract
Prevalence of inflammatory bowel disease has been on the rise in recent years, especially in pediatric populations. This study aimed to provide precise identification and stratification of pediatric patients with diagnosed ulcerative colitis (UC) according to the severity of their condition and the prediction for standard treatment according to the specific expression of candidate miRNAs. We enrolled consecutive, therapeutically naïve, pediatric UC patients with confirmed pancolitis. We examined formalin-fixed paraffin-embedded specimens of colonic tissue for the expression of 10 selected candidate miRNAs. We performed receiver operating characteristic curve analysis, using area under the curve and a logistic regression model to evaluate the diagnostic and predictive power of the miRNA panels. Sixty patients were included in the final analysis. As a control group, 18 children without macroscopic and microscopic signs of inflammatory bowel disease were examined. The combination of three candidate miRNAs (let-7i-5p, miR-223-3p and miR-4284) enabled accurate detection of pediatric UC patients and controls. A panel of four candidate miRNAs (miR-375-3p, miR-146a-5p, miR-223-3p and miR-200b-3p) was associated with severity of UC in pediatric patients and a combination of three miRNAs (miR-21-5p, miR-192-5p and miR-194-5p) was associated with early relapse of the disease. Nine patients out of the total were diagnosed with primary sclerosing cholangitis (PSC) simultaneously with ulcerative colitis. A panel of 6 candidate miRNAs (miR-142-3p, miR-146a-5p, miR-223-3p, let-7i-5p, miR-192-5p and miR-194-5p) identified those patients with PSC. Specific combinations of miRNAs are promising tools for potential use in precise disease identification and severity and prognostic stratification in pediatric patients with ulcerative pancolitis.
Highlights
Inflammatory bowel disease (IBD) is a chronic complex disorder of the digestive system caused by multiple factors, including genetics, epigenetics, gut microbiota, environmental factors and altered immune system, the precise mechanisms underlying the pathogenesis of this disease remain unclear [1,2,3]
Initial severity of the disease was evaluated by an experienced gastroenterologist using the pediatric ulcerative colitis activity index (PUCAI)
We focused on precise identification of pediatric UC patients and, thereafter, on possible stratification for severity of disease according to specific patterns of candidate miRNAs’ expression in colonic tissue
Summary
Inflammatory bowel disease (IBD) is a chronic complex disorder of the digestive system caused by multiple factors, including genetics, epigenetics, gut microbiota, environmental factors and altered immune system, the precise mechanisms underlying the pathogenesis of this disease remain unclear [1,2,3]. Patients with ulcerative colitis (UC) and Crohn’s disease (CD) involving the colon have an 4.0/). Significant differences in clinical manifestation, possible pathophysiology and treatment between children and adults prevent extrapolation of knowledge from one group to the other [8]. Therapeutically naïve patients often show quite different responses to the treatment given [10,11]. Specific deregulation patterns of ncRNAs have been linked to the pathogenesis of adult and pediatric IBD [12]
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