Epstein-Barr virus replication linked to B cell proliferation in inflamed areas of colonic mucosa of patients with inflammatory bowel disease

Sumathi Sankaran-Walters, Kanat Ransibrahmanakul, Irina Grishina, Jason Hung, Enrique Martinez, Thomas P Prindiville, Satya Dandekar

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Epstein-Barr virus (EBV) infection is associated with increased disease severity in therapeutically immunosuppressed IBD patients. The role of EBV infection in patients with IBD who are unresponsive to medical therapy is unclear. Anti-viral strategies may be a viable treatment option if severity of EBV infection, reflected in peripheral blood, contributes to IBD progression. Objectives: We investigated the role of EBV in IBD patients unresponsive to medical therapy by examining EBV reactivation and B-cell proliferation in colonic mucosa. Study design: EBV DNA copy numbers were measured by real-time PCR in peripheral blood mononuclear cells (PBMC) of 84 patients with IBD and 115 non-IBD controls in a retrospective cross-sectional study. EBV-infected cells in colonic mucosa were identified by immunohistochemistry. Results: EBV load in PBMC was higher in patients with IBD than in non-IBD controls, especially in patients not responding to medication. Inflamed colonic mucosa of these patients had high levels of expression of lytic and latent EBV genes that localized to proliferating B-lymphocytes, which was not seen in patients responding to therapy. Conclusions: EBV replication was associated with severe IBD and mucosal inflammation. Increased proliferation and EBV infection of B-lymphocytes in inflamed colonic mucosa highlight the potential role of EBV in mucosal inflammation. The immunomodulatory effects of EBV could delay the resolution of the IBD associated inflammation, thus contributing to disease progression. These results indicate that anti-viral therapeutic strategies for the resolution of IBD may be useful.

Original languageEnglish (US)
Pages (from-to)31-36
Number of pages6
JournalJournal of Clinical Virology
Volume50
Issue number1
DOIs
StatePublished - Jan 2011

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Virus Replication
Human Herpesvirus 4
Inflammatory Bowel Diseases
Mucous Membrane
B-Lymphocytes
Cell Proliferation
Epstein-Barr Virus Infections
Inflammation
Disease Progression
Blood Cells
Therapeutics
Gastrointestinal Tract
Real-Time Polymerase Chain Reaction
Cross-Sectional Studies
Immunohistochemistry
DNA

Keywords

  • Epstein-Barr virus
  • Inflammatory bowel disease
  • Mucosa
  • Refractory disease
  • Viral load

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Epstein-Barr virus replication linked to B cell proliferation in inflamed areas of colonic mucosa of patients with inflammatory bowel disease. / Sankaran-Walters, Sumathi; Ransibrahmanakul, Kanat; Grishina, Irina; Hung, Jason; Martinez, Enrique; Prindiville, Thomas P; Dandekar, Satya.

In: Journal of Clinical Virology, Vol. 50, No. 1, 01.2011, p. 31-36.

Research output: Contribution to journalArticle

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abstract = "Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Epstein-Barr virus (EBV) infection is associated with increased disease severity in therapeutically immunosuppressed IBD patients. The role of EBV infection in patients with IBD who are unresponsive to medical therapy is unclear. Anti-viral strategies may be a viable treatment option if severity of EBV infection, reflected in peripheral blood, contributes to IBD progression. Objectives: We investigated the role of EBV in IBD patients unresponsive to medical therapy by examining EBV reactivation and B-cell proliferation in colonic mucosa. Study design: EBV DNA copy numbers were measured by real-time PCR in peripheral blood mononuclear cells (PBMC) of 84 patients with IBD and 115 non-IBD controls in a retrospective cross-sectional study. EBV-infected cells in colonic mucosa were identified by immunohistochemistry. Results: EBV load in PBMC was higher in patients with IBD than in non-IBD controls, especially in patients not responding to medication. Inflamed colonic mucosa of these patients had high levels of expression of lytic and latent EBV genes that localized to proliferating B-lymphocytes, which was not seen in patients responding to therapy. Conclusions: EBV replication was associated with severe IBD and mucosal inflammation. Increased proliferation and EBV infection of B-lymphocytes in inflamed colonic mucosa highlight the potential role of EBV in mucosal inflammation. The immunomodulatory effects of EBV could delay the resolution of the IBD associated inflammation, thus contributing to disease progression. These results indicate that anti-viral therapeutic strategies for the resolution of IBD may be useful.",
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