Han-Chen Ho

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

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.

Electron microscopic characteristics of interstitial cystitis/bladder pain syndrome and their association with clinical condition

Background Electron microscopy (EM) characteristics of the urothelium in interstitial cystitis/bladder pain syndrome (IC/BPS) and their association with clinical condition are unclear. Methods Ten IC/BPS patients who were admitted for hydrodistention and 5 patients with stress urinary incontinence (control patients) were enrolled. All patients provided detailed clinical histories and underwent urodynamic studies. Cystoscopic bladder biopsies were obtained and processed for transmission EM (TEM) and scanning EM (SEM). The severity of the urothelium findings was graded on a 4-point scale (0: none, 1: mild, 2: moderate, and 3: severe). The EM findings between IC/BPS and control patients were compared; the results were analyzed using the chi-square test. Results Compared with the urothelium of control patients, the urothelium of IC/BPS patients had more severe defects of the urothelial cell layers and integrity of umbrella cells in TEM (p = 0.045 and 0.01, respectively). In SEM, umbrella cell pleomorphism increased and microplicae of the cell membrane decreased in the IC/BPS group, and both were more severe than in the control group (p = 0.022 and 0.007, respectively). The patients with moderate to severe defects of umbrella cell integrity had more severe bladder pain and smaller maximal bladder capacity (MBC) (both p = 0.010). Patients with moderate to severe defects in microplicae of the cell membrane had smaller cystometric bladder capacity and MBC (p = 0.037 and 0.047, respectively). Conclusions The results revealed significant urothelium defects in IC/BPS, especially in the umbrella cells. Defects of umbrella cells may play an important role in the pathogenesis of IC/BPS.