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Circulating MicroRNA Is a Biomarker of Pediatric Crohn Disease

Zahm, Adam M*; Thayu, Meena*; Hand, Nicholas J*; Horner, Amber*; Leonard, Mary B; Friedman, Joshua R*

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e31822200cc
Rapid Communication
Abstract

Objective: The gold standard for the diagnosis and evaluation of Crohn disease (CD) is endoscopy/colonoscopy, although this is invasive, costly, and associated with risks to the patient. Recently, circulating microRNAs (miRNAs) have emerged as promising noninvasive biomarkers. Here, we examined the utility of serum miRNAs as biomarkers of CD in children.

Patients and Methods: Studies were conducted using sera samples from patients with pediatric CD, healthy controls, and a comparison group of patients with pediatric celiac disease. Serum miRNA levels were explored initially using a microfluidic quantitative reverse transcription-polymerase chain reaction array platform. Findings were subsequently validated using quantitative reverse transcription-polymerase chain reaction in larger validation sample sets. The diagnostic utility of CD-associated serum miRNA was examined using receiver operating characteristic analysis.

Results: A survey of miRNA levels in the sera of control and patients with CD detected significant elevation of 24 miRNAs, 11 of which were chosen for further validation. All of the candidate biomarker miRNAs were confirmed in an independent CD sample set (n = 46). To explore the specificity of the CD-associated miRNAs, they were measured in the sera of patients with celiac disease (n = 12); none were changed compared with healthy controls. Receiver operating characteristic analyses revealed that serum miRNAs have promising diagnostic utility, with sensitivities for CD above 80%. Significant decreases in serum miRNAs were observed in 24 incident patients with pediatric CD after 6 months of treatment.

Conclusions: The present study identifies 11 CD-associated serum miRNA with encouraging diagnostic potential. Our findings suggest serum miRNAs may prove useful as noninvasive biomarkers in CD.

Author Information

*Division of Gastroenterology and Nutrition, USA

Division of Nephrology, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Received 15 April, 2011

Accepted 27 April, 2011

Address correspondence and reprint requests to Joshua R. Friedman, ARC 902G, 3615 Civic Center Blvd, Philadelphia, PA 19104 (e-mail: friedmanjo@email.chop.edu).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).

The study was supported by NIH R01DK079881, NIH K23DK082012, NIH R01KD60030, NIH K24 DK076808, and the Crohn's and Colitis Foundation of America.

The authors report no conflicts of interest.

Copyright 2011 by ESPGHAN and NASPGHAN