title: Circulating microRNA is a biomarker of pediatric Crohn disease.
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.
  
  
  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.
authors.affiliation: Division of Gastroenterology and Nutrition, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zahm
authors.forename: Meena
authors.initials: M
authors.lastname: Thayu
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hand
authors.forename: Amber
authors.initials: A
authors.lastname: Horner
authors.forename: Mary B
authors.initials: MB
authors.lastname: Leonard
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Friedman
mesh_terms: D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002648:Child; D003424:Crohn Disease / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D015536:Down-Regulation / Q000187:drug effects; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D046210:Microfluidic Analytical Techniques; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D007166:Immunosuppressive Agents; D035683:MicroRNAs