Epstein-Barr Virus as a Potential Etiology of Persistent Bladder Inflammation in Human Interstitial Cystitis/Bladder Pain Syndrome

Abstract

Purpose: Interstitial cystitis/bladder pain syndrome is characterized by bladder inflammation without bacterial infection. Although viral infection is a potential etiological cause, few studies have been reported.

Materials and methods: Bladder specimens were obtained from patients with interstitial cystitis/bladder pain syndrome and from patients with stress urinary incontinence as controls. Bladder specimens were tested for Epstein-Barr encoded RNAs by in situ hybridization and for Epstein-Barr DNA by quantitative real-time polymerase chain reaction, serology and immunohistochemical staining.

Results: Enrolled in study were 16 patients with interstitial cystitis/bladder pain syndrome and Hunner lesions, 23 without interstitial cystitis/bladder pain syndrome or Hunner lesions and 10 controls. The positive rate of Epstein-Barr encoded RNA on in situ hybridization in bladder specimens from patients with vs without interstitial cystitis/bladder pain syndrome and Hunner lesions was 50% vs 8.6%. No Epstein-Barr encoded RNA was found in control specimens. On quantitative real-time polymerase chain reaction Epstein-Barr DNA was detected in 68.8% vs 16.7% of bladder specimens in patients with vs without interstitial cystitis/bladder pain syndrome and Hunner lesions. The median viral load was 1,836 copies per ml (range 216 to 75,144). Only 1 control specimen was Epstein-Barr positive on quantitative real-time polymerase chain reaction. All serum samples from patients with interstitial cystitis/bladder pain syndrome showed past Epstein-Barr viral infection. Epstein-Barr infection was present in 87.5% vs 17.4% of bladder specimens from patients with vs without interstitial cystitis/bladder pain syndrome and Hunner lesions for a total of 46.2% with interstitial cystitis/bladder pain syndrome. Immunohistochemical staining of CD3 and CD20 revealed that Epstein-Barr infection was mainly restricted to T lymphocytes in bladders showing interstitial cystitis/bladder pain syndrome.

Conclusions: Bladder Epstein-Barr infection in T cells may be linked to the pathogenesis of persistent inflammation in patients with interstitial cystitis/bladder pain syndrome.

Keywords: Epstein-Barr virus infections; T-lymphocytes; cystitis; etiology; interstitial; urinary bladder.