We systematically characterized gene expression, inflammation and neovascularization in patients with interstitial cystitis/bladder pain syndrome to obtain biological evidence supporting diagnosis and classification.
We sequenced RNA obtained from bladder mucosal biopsies of 33 patients with 3 subtypes of interstitial cystitis/bladder pain syndrome, including Hunner lesions in 12, no Hunner lesions in 11 but with glomerulations and neither Hunner lesions nor glomerulations in 10, and 9 controls. Differentially expressed genes of each subtype were searched to identify subtype specific biological pathways and candidate genes important for pathogenesis. Candidate genes were validated by quantitative polymerase chain reaction and immunohistochemistry. Digital immunohistochemical quantification was performed to assess subepithelial lymphoplasmacytic cell and microvessel density. Relationships between candidate gene over expression and symptom severity were explored.
Patients with Hunner lesions showed a distinct gene expression profile associated with significant up-regulation of biological processes involving immune responses and infection, and an increase in subepithelial lymphoplasmacytic cell and microvessel density. Over expression of 2 candidate genes, VEGF and BAFF, correlated with symptom severity. Meanwhile, the gene expression profiles of patients with the 2 subtypes without Hunner lesions were similar to those of controls. No difference in biological pathways or subepithelial lymphoplasmacytic cell and microvessel density were detected between these 2 subtypes and controls.
Interstitial cystitis/bladder pain syndrome with Hunner lesions shows distinct genomic and histological features associated with immune responses and infection. In addition, VEGF and BAFF are potential disease biomarkers and therapeutic targets. This subtype should be considered separate from the syndrome.
The Journal of urology. 2019 Jul 08 [Epub]
Yoshiyuki Akiyama, Daichi Maeda, Hiroto Katoh, Teppei Morikawa, Aya Niimi, Akira Nomiya, Yusuke Sato, Taketo Kawai, Akiteru Goto, Tetsuya Fujimura, Hiroshi Fukuhara, Tohru Nakagawa, Yasuhiko Igawa, Shumpei Ishikawa, Masashi Fukayama, Haruki Kume, Yukio Homma
Department of Urology, Graduate School of Medicine, University of Tokyo , Tokyo., Department of Clinical Genomics, Graduate School of Medicine, Osaka University , Osaka., Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University , Tokyo., Department of Diagnostic Pathology, NTT Medical Center Tokyo , Tokyo., Department of Urology, National Center for Global Health and Medicine , Tokyo., Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University , Akita., Department of Urology, Jichi Medical University , Tochigi , Japan., Kyorin University School of Medicine , Tokyo., Teikyo University School of Medicine , Tokyo., Department of Continence Medicine, Graduate School of Medicine, University of Tokyo , Tokyo., Department of Pathology, Graduate School of Medicine, University of Tokyo , Tokyo., Japanese Red Cross Medical Center , Tokyo.