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PD02-07 MOLECULAR CHARACTERIZATION OF CHRONIC INFLAMMATORY DISEASES OF THE URINARY BLADDER BASED ON NEXT-GENERATION RNA SEQUENCING AND DIGITAL IMAGE ANALYSIS
Abstract   Peer reviewed

PD02-07 MOLECULAR CHARACTERIZATION OF CHRONIC INFLAMMATORY DISEASES OF THE URINARY BLADDER BASED ON NEXT-GENERATION RNA SEQUENCING AND DIGITAL IMAGE ANALYSIS

Yoshiyuki Akiyama, Jimpei Miyakawa, Masafumi Horie, Tetsuichi Saito, Tomonori Minagawa, Haruki Kume, Yukio Homma, Yi Luo and Daichi Maeda
The Journal of urology, Vol.215(5S), p.e13
05/2026
DOI: 10.1097/01.JU.0001191260.74872.fd.07

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Abstract

INTRODUCTION AND OBJECTIVES: This study aimed to elucidate distinct cellular and immunological characteristics associated with chronic inflammatory conditions of the urinary bladder, including Hunner-type interstitial cystitis (HIC), bacillus Calmette–Guérin (BCG)-related cystitis, follicular cystitis (FC), and chronic bacterial cystitis (CBC), by next-generation RNA-sequencing and digital image analysis. METHODS: Mucosal bladder biopsies of HIC (n=21), BCG cystitis (n=13), FC (n=5), or CBC (n=3) were subjected to RNA sequencing and quantitative polymerase chain reaction for key genes involved in adaptive immune responses. Digital immunohistochemical quantification was performed to evaluate and compare the degree of urothelial denudation and the density of infiltrating T-lymphocytes, B-lymphocytes, mast cells, and plasma cells. RESULTS: HIC specimens exhibited a markedly distinct transcriptional profile (Figure 1), with 3,566 differentially expressed genes and enrichment of 116 biological processes particularly associated with microbial response and heightened autoimmunity with Th1/Th17 axis polarization. HIC samples showed significantly increased levels of mRNA expression for genes associated with Th1-immune responses (specifically, IL12A/B, IFNG, and TBX21). Histologically, the density of IL-17-positive cells, epithelial denudation, and plasma cell ratio were significantly higher in HIC bladders than other types of cystitis, while there was no difference in the densities of lymphoplasmacytic and mast cells, or in B cell ratio between the groups (Figure 2). CONCLUSIONS: HIC inflammation is characterized by increased plasma cell infiltration in the context of a Th1/17-polarized immune environment, coupled with epithelial denudation. These findings provide a platform for development of novel treatment strategies, and facilitate basic research into the pathophysiology of this enigmatic disease.

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