β-Defensin 2, an Antimicrobial Peptide, as a Novel Biomarker for Ulcerative Interstitial Cystitis; Can β-Defensin 2 Suspect the Dysbiosis of Urine Microbiota?

Sang Wook Lee,Young Ho Kim,Si Hyun Kim,Hae Woong Choi,Kwang Woo Lee,Ji Eun Moon,Ahrim Moon,Woong Bin Kim

doi:10.3390/diagnostics11112082

Abstract

As urine is not sterile, inflammatory reactions caused by dysbiosis of the urinary microbiota may induce interstitial cystitis. A study was conducted to determine whether β-defensin 2 (BD-2), a specific antimicrobial peptide in the bladder, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC). Urine samples from three female groups were examined: healthy controls (n = 34, Control group), non-Hunner type IC (n = 40, NHIC group), and Hunner type IC (n = 68, HIC group). Urine samples were collected via a transurethral catheter and assayed for BD-2 levels using enzyme linked immunosorbent assay. Under general or regional anesthesia, cystoscopy with diagnostic and therapeutic hydrodistension was performed in NHIC and HIC groups patients. These patients underwent a biopsy of the bladders. Based on the urinary specimens from 142 patients, BD-2 expression was found to be 18-fold higher in patients with Hunner type IC than in patients with non-Hunner type IC. The enhanced secretion of BD-2 exhibited a strong correlation with increased mast cell counts associated with bladder IC pathology. Enhanced urinary secretion of the antimicrobial peptide BD-2 from Hunner type IC patients associated with clinical phenotypes and demonstrated relatively robust levels to be used as a potential biomarker. Moreover, the increased urinary level of BD-2 may suggest a new possibility of biomarkers caused by dysbiosis of the urinary microbiota in ulcerative IC.

Highlights

Interstitial cystitis/bladder pain syndrome (IC/BPS) is traditionally defined as a chronic inflammatory disease with no definite cause of bacterial infection and is characterized by pain when the bladder is full and voiding; symptoms include changes in urination frequency and urgency [1]
No significant difference was detected between Control and NHIC groups, but significant differences were observed between Control and HIC groups and between NHIC and HIC group
Our study demonstrated that patients with ulcerative interstitial cystitis (IC) produced robustly higher mast cell counts and urinary BD-2 than that produced by patients with non-ulcerative IC

Summary

Introduction

Interstitial cystitis/bladder pain syndrome (IC/BPS) is traditionally defined as a chronic inflammatory disease with no definite cause of bacterial infection and is characterized by pain when the bladder is full and voiding; symptoms include changes in urination frequency and urgency [1]. The IC/BPS definition is in agreement with the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction: “An unpleasant sensation (pain, pressure, and discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms, persisting for more than six weeks in the absence of infection or other identifiable causes”. This criterion was chosen because it enables therapy to begin after a relatively short duration of symptoms, avoiding delay in treatment that might occur with longer symptom duration criteria (i.e., six months). It is understood that these traditional urine culture tools are inadequate for studying bacteria in patients with IC/BPS and presumed cystitis associated with chronic covert bacteria

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Conclusion