title: Blood-based biomarkers used to predict disease activity in Crohn's disease and ulcerative colitis.
abstract: BACKGROUND
  Identifying specific genes that are differentially expressed during inflammatory bowel disease flares may help stratify disease activity. The aim of this study was to identify panels of genes to be able to distinguish disease activity in Crohn's disease (CD) and ulcerative colitis (UC).
  
  
  METHODS
  Patients were grouped into categories based on disease and severity determined by histological grading. Whole blood was collected by PAXgene Blood RNA collection tubes, (PreAnalytiX) and gene expression analysis using messenger RNA was conducted. Logistic regression was performed on multiple combinations of common probe sets, and data were evaluated in terms of discrimination by computing the area under the receiving operator characteristic curve (ROC-AUC).
  
  
  RESULTS
  Nine inactive CD, 8 mild CD, 10 moderate-to-severe CD, 9 inactive UC, 8 mild UC, 10 moderate-to-severe UC, and 120 controls were hybridized to Affymetrix U133 Plus 2 microarrays. Panels of 6 individual genes discriminated the stages of disease activity: CD with mild severity {ROC-AUC, 0.89 (95% confidence interval [CI], 0.84%-0.95%)}, CD with moderate-to-severe severity (ROC-AUC 0.98 [95% CI, 0.97-1.0]), UC with mild severity (ROC-AUC 0.92 [95% CI, 0.87-0.96]), and UC with moderate-to-severe severity (ROC-AUC 0.99 [95% CI, 0.97-1.0]). Validation by real-time reverse transcription-PCR confirmed the Affymetrix microarray data.
  
  
  CONCLUSIONS
  The specific whole blood gene panels reliably distinguished CD and UC and determined the activity of disease, with high sensitivity and specificity in our cohorts of patients. This simple serological test has the potential to become a biomarker to determine the activity of disease.
authors.affiliation: *Division of Gastroenterology and Hepatology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; †Division of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California; ‡Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; §Sentinel Center, SBC, Shanghai, China; ‖GoldenHealthDx, Ontario, Canada; and ¶GeneNews, Toronto, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Burakoff
authors.forename: Vikas
authors.initials: V
authors.lastname: Pabby
authors.forename: Louisa
authors.initials: L
authors.lastname: Onyewadume
authors.forename: Robert
authors.initials: R
authors.lastname: Odze
authors.forename: Cheryl
authors.initials: C
authors.lastname: Adackapara
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Sonia
authors.initials: S
authors.lastname: Friedman
authors.forename: Matthew
authors.initials: M
authors.lastname: Hamilton
authors.forename: Joshua
authors.initials: J
authors.lastname: Korzenik
authors.forename: Jonathan
authors.initials: J
authors.lastname: Levine
authors.forename: Frederick
authors.initials: F
authors.lastname: Makrauer
authors.forename: Changming
authors.initials: C
authors.lastname: Cheng
authors.forename: Hai Choo
authors.initials: HC
authors.lastname: Smith
authors.forename: Choong-Chin
authors.initials: CC
authors.lastname: Liew
authors.forename: Samuel
authors.initials: S
authors.lastname: Chao
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger