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Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis

BACKGROUND: The precise role of cytomegalovirus (CMV) in ulcerative colitis (UC) remains disputed. We evaluated the association of CMV-specific host immune responses and systemic or local viral replication with responses to systemic steroids in patients with moderate to severe UC. METHODS: Patients...

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Autores principales: Jung, Kyung Hwa, Kim, Jihun, Lee, Ho-Su, Choi, Jene, Jang, Se Jin, Jung, Jiwon, Kim, Min Jae, Chong, Yong Pil, Lee, Sang-Oh, Choi, Sang-Ho, Kim, Yang Soo, Woo, Jun Hee, Park, Sang Hyoung, Yang, Dong-Hoon, Ye, Byong Duk, Yang, Suk-Kyun, Kim, Sung-Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934884/
https://www.ncbi.nlm.nih.gov/pubmed/31893211
http://dx.doi.org/10.1093/ofid/ofz526
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author Jung, Kyung Hwa
Kim, Jihun
Lee, Ho-Su
Choi, Jene
Jang, Se Jin
Jung, Jiwon
Kim, Min Jae
Chong, Yong Pil
Lee, Sang-Oh
Choi, Sang-Ho
Kim, Yang Soo
Woo, Jun Hee
Park, Sang Hyoung
Yang, Dong-Hoon
Ye, Byong Duk
Yang, Suk-Kyun
Kim, Sung-Han
author_facet Jung, Kyung Hwa
Kim, Jihun
Lee, Ho-Su
Choi, Jene
Jang, Se Jin
Jung, Jiwon
Kim, Min Jae
Chong, Yong Pil
Lee, Sang-Oh
Choi, Sang-Ho
Kim, Yang Soo
Woo, Jun Hee
Park, Sang Hyoung
Yang, Dong-Hoon
Ye, Byong Duk
Yang, Suk-Kyun
Kim, Sung-Han
author_sort Jung, Kyung Hwa
collection PubMed
description BACKGROUND: The precise role of cytomegalovirus (CMV) in ulcerative colitis (UC) remains disputed. We evaluated the association of CMV-specific host immune responses and systemic or local viral replication with responses to systemic steroids in patients with moderate to severe UC. METHODS: Patients who were hospitalized for moderate to severe UC between April 2015 and June 2016 were enrolled. At baseline, all enrolled patients underwent CMV-specific enzyme-linked immunospot assays, quantitative polymerase chain reaction (qPCR) analysis of blood and colonic tissue for CMV viral load, histopathological testing for CMV in colonic tissue by hematoxylin and eosin staining, and immunohistochemical (IHC) analysis. Clinical responses to steroid therapy based on the Oxford index were assessed on day 3. RESULTS: Of the 80 patients evaluated, 28 (35.0%) had poor responses to steroid therapy on day 3 of intensive treatment. The presence of inclusion bodies (32.1%) and high-grade (≥3) positivity on IHC (50.0%), as well as colonic (mean 1440.4 copies/mg) and blood (mean, 3692.6 copies/mL) CMV viral load, were higher in steroid-refractory UC patients than the control group (13.5%, 1.9%, mean 429.2 copies/mg, and mean 231.2 copies/mL, respectively; P = .046, .009, .017, and .002, respectively). However, CMV-specific T-cell responses were not associated with steroid-refractory UC. Multivariate analysis revealed that a higher Mayo score (odds ratio [OR], 2.00; P = .002) and higher blood CMV viral load via qPCR analysis (OR, 3.58; P = .044) were independent risk factors for steroid-refractory UC. CONCLUSIONS: In patients with moderate to severe UC, higher Mayo score and blood CMV expression determined by qPCR are independently associated with steroid refractoriness. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT 02439372.
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spelling pubmed-69348842019-12-31 Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis Jung, Kyung Hwa Kim, Jihun Lee, Ho-Su Choi, Jene Jang, Se Jin Jung, Jiwon Kim, Min Jae Chong, Yong Pil Lee, Sang-Oh Choi, Sang-Ho Kim, Yang Soo Woo, Jun Hee Park, Sang Hyoung Yang, Dong-Hoon Ye, Byong Duk Yang, Suk-Kyun Kim, Sung-Han Open Forum Infect Dis Major Article BACKGROUND: The precise role of cytomegalovirus (CMV) in ulcerative colitis (UC) remains disputed. We evaluated the association of CMV-specific host immune responses and systemic or local viral replication with responses to systemic steroids in patients with moderate to severe UC. METHODS: Patients who were hospitalized for moderate to severe UC between April 2015 and June 2016 were enrolled. At baseline, all enrolled patients underwent CMV-specific enzyme-linked immunospot assays, quantitative polymerase chain reaction (qPCR) analysis of blood and colonic tissue for CMV viral load, histopathological testing for CMV in colonic tissue by hematoxylin and eosin staining, and immunohistochemical (IHC) analysis. Clinical responses to steroid therapy based on the Oxford index were assessed on day 3. RESULTS: Of the 80 patients evaluated, 28 (35.0%) had poor responses to steroid therapy on day 3 of intensive treatment. The presence of inclusion bodies (32.1%) and high-grade (≥3) positivity on IHC (50.0%), as well as colonic (mean 1440.4 copies/mg) and blood (mean, 3692.6 copies/mL) CMV viral load, were higher in steroid-refractory UC patients than the control group (13.5%, 1.9%, mean 429.2 copies/mg, and mean 231.2 copies/mL, respectively; P = .046, .009, .017, and .002, respectively). However, CMV-specific T-cell responses were not associated with steroid-refractory UC. Multivariate analysis revealed that a higher Mayo score (odds ratio [OR], 2.00; P = .002) and higher blood CMV viral load via qPCR analysis (OR, 3.58; P = .044) were independent risk factors for steroid-refractory UC. CONCLUSIONS: In patients with moderate to severe UC, higher Mayo score and blood CMV expression determined by qPCR are independently associated with steroid refractoriness. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT 02439372. Oxford University Press 2019-12-18 /pmc/articles/PMC6934884/ /pubmed/31893211 http://dx.doi.org/10.1093/ofid/ofz526 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Article
Jung, Kyung Hwa
Kim, Jihun
Lee, Ho-Su
Choi, Jene
Jang, Se Jin
Jung, Jiwon
Kim, Min Jae
Chong, Yong Pil
Lee, Sang-Oh
Choi, Sang-Ho
Kim, Yang Soo
Woo, Jun Hee
Park, Sang Hyoung
Yang, Dong-Hoon
Ye, Byong Duk
Yang, Suk-Kyun
Kim, Sung-Han
Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis
title Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis
title_full Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis
title_fullStr Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis
title_full_unstemmed Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis
title_short Clinical Implications of the CMV-Specific T-Cell Response and Local or Systemic CMV Viral Replication in Patients With Moderate to Severe Ulcerative Colitis
title_sort clinical implications of the cmv-specific t-cell response and local or systemic cmv viral replication in patients with moderate to severe ulcerative colitis
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934884/
https://www.ncbi.nlm.nih.gov/pubmed/31893211
http://dx.doi.org/10.1093/ofid/ofz526
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