<p>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). Transcriptomic analyses using next-generation RNA sequencing, along with quantitative polymerase chain reaction, were performed on mucosal bladder biopsies to assess the whole transcriptional and immune-response profiles. Furthermore, digital immunohistochemical quantification evaluated urothelial denudation and the densities of infiltrating immune cells, including T-lymphocytes, B-lymphocytes, mast cells, and plasma cells. HIC specimens exhibited a markedly distinct transcriptional profile, 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. Histologically, HIC bladders demonstrated significant epithelial denudation, elevated IL-17-positive cell density, and increased plasma cell ratios compared to other cystitis types. No significant differences were observed in overall lymphoplasmacytic or mast cell densities, nor in B cell ratios among the groups. These findings underscore a unique immunopathological signature in HIC, characterized by plasma cell predominance within a Th1/17-polarized immune environment and epithelial denudation, offering new insights into its pathogenesis and therapeutic targeting.</p>

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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,
  • Tetsuo Ushiku,
  • Akiteru Goto,
  • Haruki Kume,
  • Yukio Homma,
  • Yi Luo,
  • Daichi Maeda

摘要

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). Transcriptomic analyses using next-generation RNA sequencing, along with quantitative polymerase chain reaction, were performed on mucosal bladder biopsies to assess the whole transcriptional and immune-response profiles. Furthermore, digital immunohistochemical quantification evaluated urothelial denudation and the densities of infiltrating immune cells, including T-lymphocytes, B-lymphocytes, mast cells, and plasma cells. HIC specimens exhibited a markedly distinct transcriptional profile, 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. Histologically, HIC bladders demonstrated significant epithelial denudation, elevated IL-17-positive cell density, and increased plasma cell ratios compared to other cystitis types. No significant differences were observed in overall lymphoplasmacytic or mast cell densities, nor in B cell ratios among the groups. These findings underscore a unique immunopathological signature in HIC, characterized by plasma cell predominance within a Th1/17-polarized immune environment and epithelial denudation, offering new insights into its pathogenesis and therapeutic targeting.