Mucosal Profiles of Immune Molecules Related to T Helper and Regulatory T Cells Predict Future Relapse in Patients with Quiescent Ulcerative Colitis

Keita Fukaura, Yoichiro Iboshi, Haruei Ogino, Eikichi Ihara, Kazuhiko Nakamura, Yuichiro Nishihara, Kei Nishioka, Takatoshi Chinen, Tsutomu Iwasa, Akira Aso, Ayako Goto, Kazuhiro Haraguchi, Hirotada Akiho, Naohiko Harada, Yoshihiro Ogawa

研究成果: ジャーナルへの寄稿記事

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Background: T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown. Methods: The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses. Results: Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001). Conclusions: The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care.

元の言語英語
ページ(範囲)1019-1027
ページ数9
ジャーナルInflammatory bowel diseases
25
発行部数6
DOI
出版物ステータス出版済み - 1 1 2019

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Regulatory T-Lymphocytes
Helper-Inducer T-Lymphocytes
Ulcerative Colitis
Interleukin-17
Recurrence
Kaplan-Meier Estimate
Patient Care
Mucous Membrane
Transcription Factors
Up-Regulation
Multivariate Analysis
Cytokines
Biopsy
Gene Expression
Polymerase Chain Reaction
interleukin-21

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

これを引用

Mucosal Profiles of Immune Molecules Related to T Helper and Regulatory T Cells Predict Future Relapse in Patients with Quiescent Ulcerative Colitis. / Fukaura, Keita; Iboshi, Yoichiro; Ogino, Haruei; Ihara, Eikichi; Nakamura, Kazuhiko; Nishihara, Yuichiro; Nishioka, Kei; Chinen, Takatoshi; Iwasa, Tsutomu; Aso, Akira; Goto, Ayako; Haraguchi, Kazuhiro; Akiho, Hirotada; Harada, Naohiko; Ogawa, Yoshihiro.

:: Inflammatory bowel diseases, 巻 25, 番号 6, 01.01.2019, p. 1019-1027.

研究成果: ジャーナルへの寄稿記事

Fukaura, K, Iboshi, Y, Ogino, H, Ihara, E, Nakamura, K, Nishihara, Y, Nishioka, K, Chinen, T, Iwasa, T, Aso, A, Goto, A, Haraguchi, K, Akiho, H, Harada, N & Ogawa, Y 2019, 'Mucosal Profiles of Immune Molecules Related to T Helper and Regulatory T Cells Predict Future Relapse in Patients with Quiescent Ulcerative Colitis', Inflammatory bowel diseases, 巻. 25, 番号 6, pp. 1019-1027. https://doi.org/10.1093/ibd/izy395
Fukaura, Keita ; Iboshi, Yoichiro ; Ogino, Haruei ; Ihara, Eikichi ; Nakamura, Kazuhiko ; Nishihara, Yuichiro ; Nishioka, Kei ; Chinen, Takatoshi ; Iwasa, Tsutomu ; Aso, Akira ; Goto, Ayako ; Haraguchi, Kazuhiro ; Akiho, Hirotada ; Harada, Naohiko ; Ogawa, Yoshihiro. / Mucosal Profiles of Immune Molecules Related to T Helper and Regulatory T Cells Predict Future Relapse in Patients with Quiescent Ulcerative Colitis. :: Inflammatory bowel diseases. 2019 ; 巻 25, 番号 6. pp. 1019-1027.
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title = "Mucosal Profiles of Immune Molecules Related to T Helper and Regulatory T Cells Predict Future Relapse in Patients with Quiescent Ulcerative Colitis",
abstract = "Background: T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown. Methods: The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses. Results: Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001). Conclusions: The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care.",
author = "Keita Fukaura and Yoichiro Iboshi and Haruei Ogino and Eikichi Ihara and Kazuhiko Nakamura and Yuichiro Nishihara and Kei Nishioka and Takatoshi Chinen and Tsutomu Iwasa and Akira Aso and Ayako Goto and Kazuhiro Haraguchi and Hirotada Akiho and Naohiko Harada and Yoshihiro Ogawa",
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T1 - Mucosal Profiles of Immune Molecules Related to T Helper and Regulatory T Cells Predict Future Relapse in Patients with Quiescent Ulcerative Colitis

AU - Fukaura, Keita

AU - Iboshi, Yoichiro

AU - Ogino, Haruei

AU - Ihara, Eikichi

AU - Nakamura, Kazuhiko

AU - Nishihara, Yuichiro

AU - Nishioka, Kei

AU - Chinen, Takatoshi

AU - Iwasa, Tsutomu

AU - Aso, Akira

AU - Goto, Ayako

AU - Haraguchi, Kazuhiro

AU - Akiho, Hirotada

AU - Harada, Naohiko

AU - Ogawa, Yoshihiro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown. Methods: The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses. Results: Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001). Conclusions: The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care.

AB - Background: T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown. Methods: The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses. Results: Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001). Conclusions: The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care.

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U2 - 10.1093/ibd/izy395

DO - 10.1093/ibd/izy395

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AN - SCOPUS:85065654992

VL - 25

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JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

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