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

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

研究成果: ジャーナルへの寄稿記事

19 引用 (Scopus)

抄録

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-g, 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.

元の言語英語
ページ(範囲)967-977
ページ数11
ジャーナルInflammatory bowel diseases
20
発行部数6
DOI
出版物ステータス出版済み - 6 2014

Fingerprint

Intestinal Mucosa
Helper-Inducer T-Lymphocytes
Ulcerative Colitis
Crohn Disease
Area Under Curve
Principal Component Analysis
Inflammatory Bowel Diseases
Genes
Interleukin-12 Subunit p35
Interleukin-13
Discriminant Analysis
Regulatory T-Lymphocytes
Ileum
ROC Curve
Interferons
Colon
Mucous Membrane
Transcription Factors
Cytokines
Biopsy

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

これを引用

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; Nakamura, Kazuhiko; Ihara, Eikichi; Iwasa, Tsutomu; Akiho, Hirotada; Harada, Naohiko; Nakamuta, Makoto; Takayanagi, Ryoichi.

:: Inflammatory bowel diseases, 巻 20, 番号 6, 06.2014, p. 967-977.

研究成果: ジャーナルへの寄稿記事

Iboshi, Yoichiro ; Nakamura, Kazuhiko ; Ihara, Eikichi ; Iwasa, Tsutomu ; Akiho, Hirotada ; Harada, Naohiko ; Nakamuta, Makoto ; Takayanagi, Ryoichi. / 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. :: Inflammatory bowel diseases. 2014 ; 巻 20, 番号 6. pp. 967-977.
@article{f77a530372e44a5cb2ec7aa386dfc8ae,
title = "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",
abstract = "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-g, 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.",
author = "Yoichiro Iboshi and Kazuhiko Nakamura and Eikichi Ihara and Tsutomu Iwasa and Hirotada Akiho and Naohiko Harada and Makoto Nakamuta and Ryoichi Takayanagi",
year = "2014",
month = "6",
doi = "10.1097/MIB.0000000000000028",
language = "English",
volume = "20",
pages = "967--977",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - 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

AU - Iboshi, Yoichiro

AU - Nakamura, Kazuhiko

AU - Ihara, Eikichi

AU - Iwasa, Tsutomu

AU - Akiho, Hirotada

AU - Harada, Naohiko

AU - Nakamuta, Makoto

AU - Takayanagi, Ryoichi

PY - 2014/6

Y1 - 2014/6

N2 - 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-g, 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.

AB - 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-g, 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.

UR - http://www.scopus.com/inward/record.url?scp=84902162746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902162746&partnerID=8YFLogxK

U2 - 10.1097/MIB.0000000000000028

DO - 10.1097/MIB.0000000000000028

M3 - Article

C2 - 24739631

AN - SCOPUS:84902162746

VL - 20

SP - 967

EP - 977

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 6

ER -