Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318280b19e
Original Clinical Article

Combined Serological, Genetic, and Inflammatory Markers Differentiate Non-IBD, Crohn's Disease, and Ulcerative Colitis Patients

Plevy, Scott MD*; Silverberg, Mark S. MD, PhD; Lockton, Steve PhD; Stockfisch, Tom PhD§; Croner, Lisa PhD; Stachelski, Jordan BS; Brown, Michelle BA; Triggs, Cheryl BS; Chuang, Emil MD; Princen, Fred PhD; Singh, Sharat PhD

Supplemental Author Material
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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.

© Crohn's & Colitis Foundation of America, Inc.

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