Refractory inflammatory bowel disease: is there a role for Epstein-Barr virus? A case-controlled study using highly sensitive Epstein-Barr virus-encoded small RNA1 in situ hybridization

Hum Pathol. 2018 Dec:82:187-192. doi: 10.1016/j.humpath.2018.08.001. Epub 2018 Aug 16.

Abstract

A potential role for viral infections has been implicated in inflammatory bowel disease (IBD) unresponsive to medical treatment. It is well known that Epstein-Barr virus (EBV) infection can elicit a brisk mononuclear response in the gastrointestinal tract. The aim of this study was to further evaluate the role of EBV in patients with refractory IBD and compare them with nonrefractory IBD cases. Surgically resected colonic specimens from 67 patients with refractory IBD (62 with ulcerative colitis, 3 patients with Crohn disease, and 2 patients with indeterminate colitis) were retrieved. Twelve colectomy specimens from patients with ulcerative colitis who had undergone resections for dysplasia or endometriosis were included as controls. Highly sensitive EBV-encoded small RNA1 (EBER-1) in situ hybridization was performed on a representative block from each specimen. EBER-1 reactivity was graded as absent, focal, or diffuse. EBV was detected in 60% (40/67) of patients with refractory IBD compared with 25% (3/12) of the control group (P < .05). Focal EBER-1 positivity was present in 45% of cases of refractory IBD compared with 25% of controls. Diffuse EBER-1 reactivity was seen in 15% of cases of refractory IBD (10/67); none of the samples from the control group contained diffuse EBER-1 positivity. There was a positive correlation between EBER positivity and depth of inflammation and mucosal ulceration in patients with refractory IBD. Our findings suggest a potential role for EBV infection in patients with refractory IBD.

Keywords: Crohn Disease; Epstein-Barr virus; Inflammatory bowel disease; Refractory; Ulcerative colitis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Case-Control Studies
  • Child
  • Colectomy
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / therapy
  • Colitis, Ulcerative / virology*
  • Colon / drug effects
  • Colon / pathology
  • Colon / surgery
  • Colon / virology*
  • Crohn Disease / diagnosis
  • Crohn Disease / therapy
  • Crohn Disease / virology*
  • Drug Resistance
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Gastrointestinal Agents / therapeutic use
  • Herpesvirus 4, Human / genetics*
  • Humans
  • In Situ Hybridization*
  • Male
  • Middle Aged
  • RNA, Viral / genetics*
  • Risk Factors
  • Severity of Illness Index
  • United States
  • Young Adult

Substances

  • Epstein-Barr virus encoded RNA 1
  • Gastrointestinal Agents
  • RNA, Viral