title: Combined serological, genetic, and inflammatory markers differentiate non-IBD, Crohn's disease, and ulcerative colitis patients.
abstract: BACKGROUND
  Previous studies have demonstrated that serological markers can assist in diagnosing inflammatory bowel disease (IBD). In this study, we aim to build a diagnostic tool incorporating serological markers, genetic variants, and markers of inflammation into a computational algorithm to examine patterns of combinations of markers to (1) identify patients with IBD and (2) differentiate patients with Crohn's disease (CD) from ulcerative colitis (UC).
  
  
  METHODS
  In this cross-sectional study, patient blood samples from 572 CD, 328 UC, 437 non-IBD controls, and 183 healthy controls from academic and community centers were analyzed for 17 markers: 8 serological markers (ASCA-IgA, ASCA-IgG, ANCA, pANCA, OmpC, CBir1, A4-Fla2, and FlaX), 4 genetic markers (ATG16L1, NKX2-3, ECM1, and STAT3), and 5 inflammatory markers (CRP, SAA, ICAM-1, VCAM-1, and VEGF). A diagnostic Random Forest algorithm was constructed to classify IBD, CD, and UC.
  
  
  RESULTS
  Receiver operating characteristic analysis compared the diagnostic accuracy of using a panel of serological markers only (ASCA-IgA, ASCA-IgG, ANCA, pANCA, OmpC, and CBir1) versus using a marker panel that in addition to the serological markers mentioned above also included gene variants, inflammatory markers, and 2 additional serological markers (A4-Fla2 and FlaX). The extended marker panel increased the IBD versus non-IBD discrimination area under the curve from 0.80 (95% confidence interval [CI], ±0.05) to 0.87 (95% CI, ±0.04; P < 0.001). The CD versus UC discrimination increased from 0.78 (95% CI, ±0.06) to 0.93 (95% CI, ±0.04; P < 0.001).
  
  
  CONCLUSIONS
  Incorporating a combination of serological, genetic, and inflammation markers into a diagnostic algorithm improved the accuracy of identifying IBD and differentiating CD from UC versus using serological markers alone.
authors.affiliation: Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. scott_plevy@med.unc.edu
authors.forename: Scott
authors.initials: S
authors.lastname: Plevy
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: Steve
authors.initials: S
authors.lastname: Lockton
authors.forename: Tom
authors.initials: T
authors.lastname: Stockfisch
authors.forename: Lisa
authors.initials: L
authors.lastname: Croner
authors.forename: Jordan
authors.initials: J
authors.lastname: Stachelski
authors.forename: Michelle
authors.initials: M
authors.lastname: Brown
authors.forename: Cheryl
authors.initials: C
authors.lastname: Triggs
authors.forename: Emil
authors.initials: E
authors.lastname: Chuang
authors.forename: Fred
authors.initials: F
authors.lastname: Princen
authors.forename: Sharat
authors.initials: S
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005819:Genetic Markers