title: Low Serum Levels of MicroRNA-19 Are Associated with a Stricturing Crohn's Disease Phenotype.
abstract: BACKGROUND
  Development of fibrosis and subsequent stricture formation in Crohn's disease (CD) increases morbidity and rates of surgery and reduces patients' quality of life. There are currently no biomarkers of intestinal fibrosis that might allow earlier identification and better management of patients at increased risk of stricture formation.
  
  
  METHODS
  MicroRNA profiling of serum from CD patients was used to identify microRNAs associated with stricture formation. Differential expression of miR-19a-3p and miR-19b-3p was validated by quantitative PCR in independent CD cohort of stricturing and nonstricturing patients (n = 46 and n = 62, respectively). Levels of miR-19a-3p and miR-19b-3p were also quantified in baseline serum samples, and expression compared between CD patients who subsequently developed stricture and those who did not (n = 11 and n = 44, respectively).
  
  
  RESULTS
  Serum levels of miR-19a-3p and miR-19b-3p in the array were lower in CD patients with a stricturing phenotype than in control CD patients (P = 0.007 and 0.008, respectively). The reduction in miR-19a-3p and 19b-3p was verified in a second cohort (P = 0.002). The association of miR-19-3p with stricturing CD was independent of potential confounding clinical variables, including disease duration, disease activity, site, gender, and age. Serum analyses in patients with 4 years of follow-up support the hypothesis that reduced miR-19a-3p and miR-19b-3p predate stricture development with a trend toward significance (P = 0.077 and P = 0.060, respectively).
  
  
  CONCLUSIONS
  These data identify miR-19-3p as a potential circulating marker of stricturing CD. Our data show that microRNAs have utility as noninvasive biomarkers of stricturing CD. Further longitudinal studies are required to determine the prognostic value of miR-19-3p at diagnosis.
authors.affiliation: *Centre for Digestive Diseases, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom; †Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom; ‡Department of Surgery and Cancer, Imperial College London, London, United Kingdom; §Centre for Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, United Kingdom; ‖Department of Cellular Pathology, The Royal London Hospital, London, United Kingdom; ¶Department of Internal Medicine, S. Matteo Hospital, University of Pavia, Pavia, Italy; and **Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Amy
authors.initials: A
authors.lastname: Lewis
authors.forename: Shameer
authors.initials: S
authors.lastname: Mehta
authors.forename: Luke N
authors.initials: LN
authors.lastname: Hanna
authors.forename: Laura A
authors.initials: LA
authors.lastname: Rogalski
authors.forename: Rosemary
authors.initials: R
authors.lastname: Jeffery
authors.forename: Anke
authors.initials: A
authors.lastname: Nijhuis
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kumagai
authors.forename: Paolo
authors.initials: P
authors.lastname: Biancheri
authors.forename: Jake G
authors.initials: JG
authors.lastname: Bundy
authors.forename: Cleo L
authors.initials: CL
authors.lastname: Bishop
authors.forename: Roger
authors.initials: R
authors.lastname: Feakins
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Sabatino
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.forename: James O
authors.initials: JO
authors.lastname: Lindsay
authors.forename: Andrew
authors.initials: A
authors.lastname: Silver
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003251:Constriction, Pathologic / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; C549214:MIRN19A microRNA, human; D035683:MicroRNAs