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

Kyung Hwa Jung; Jihun Kim; Ho-Su Lee; Jene Choi; Se Jin Jang; Jiwon Jung; Min Jae Kim; Yong Pil Chong; Sang-Oh Lee; Sang-Ho Choi; Yang Soo Kim; Jun Hee Woo; Sang Hyoung Park; Dong-Hoon Yang; Byong Duk Ye; Suk-Kyun Yang; Sung-Han Kim

doi:10.1093/ofid/ofz526

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

Open Forum Infect Dis. 2019 Dec 18;6(12):ofz526. doi: 10.1093/ofid/ofz526. eCollection 2019 Dec.

Authors

Kyung Hwa Jung¹, Jihun Kim², Ho-Su Lee³, Jene Choi², Se Jin Jang², Jiwon Jung¹, Min Jae Kim¹, Yong Pil Chong¹, Sang-Oh Lee¹, Sang-Ho Choi¹, Yang Soo Kim¹, Jun Hee Woo¹, Sang Hyoung Park^{4

5}, Dong-Hoon Yang⁴, Byong Duk Ye^{4

5}, Suk-Kyun Yang^{4

5}, Sung-Han Kim¹

Affiliations

¹ Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
² Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
³ Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁴ Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁵ Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Abstract

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.

Clinicaltrialsgov registration number: NCT02439372.

Keywords: T-cell response; cytomegalovirus; enzyme-linked immunospot; ulcerative colitis.

Associated data

ClinicalTrials.gov/NCT02439372