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Multigene Analysis Unveils Distinctive Expression Profiles of Helper T-cell–related Genes in the Intestinal Mucosa that Discriminate Between Ulcerative Colitis and Crohn's Disease

Iboshi, Yoichiro MD*; Nakamura, Kazuhiko MD, PhD*; Ihara, Eikichi MD, PhD*; Iwasa, Tsutomu MD*; Akiho, Hirotada MD, PhD*; Harada, Naohiko MD, PhD; Nakamuta, Makoto MD, PhD; Takayanagi, Ryoichi MD, PhD*

doi: 10.1097/MIB.0000000000000028
Original Basic Science Articles

Background: Although the involvement of helper T (Th) and regulatory T (Treg) cell-related immune molecules in pathogenesis of inflammatory bowel disease (IBD) is widely accepted, no discriminatory mucosal expression profiles of these molecules between ulcerative colitis (UC) and Crohn's disease (CD) have been clarified.

Methods: Mucosal expression of 17 cytokines and transcription factors related to Th1, Th2, Th17, and Treg were measured by quantitative PCR in endoscopic biopsies from inflamed (40 from UC [UCI] and 20 from CD [CDI]) and noninflamed (47, 22, and 25 from UC, CD, and controls, respectively) colon or ileum. The discriminatory power of these markers to differentiate between the 2 diseases was evaluated by linear discriminant analysis and, unsupervised, principal component analysis.

Results: By univariate analysis, many targets were markedly increased in inflamed versus noninflamed areas. However, marker expression was almost comparable between UCI and CDI, with the largest difference in UCI-predominant interleukin (IL) 21 and IL-13 with area under the receiver operating characteristic curve (AUC) values of 0.704 and 0.664, respectively. In contrast, combinations of 2 to 7 markers improved UCI versus CDI discrimination with AUC = 0.875 to 0.975. Among these, a 5-maker set (interferon-γ, IL-12 p35, T-bet, GATA3, and IL-21) demonstrated an AUC of 0.949 and a misclassification rate of 8.3%. Principal component analysis also markedly separated UCI and CDI.

Conclusions: Inflamed mucosae from UC and CD could be discriminated with high accuracy using combinations of Th cell–related markers. Multigene analysis, possibly reflecting the underlying pathogenesis, is expected to be useful for diagnosis, monitoring and further defining distinctive characteristics in inflammatory bowel disease.

Article first published online 15 April 2014.

*Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and

Department of Gastroenterology, Clinical Research Center, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.

Reprints: Kazuhiko Nakamura, MD, PhD, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan (e-mail:

Supported in part by Grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

The authors have no conflicts of interest to disclose.

Received December 27, 2013

Accepted February 12, 2014

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