Hunner-type interstitial cystitis (HIC) is a chronic inflammatory disease of the urinary bladder with an unknown etiology. We conducted comprehensive immunogenomic profiling of bladder specimens obtained by biopsy and cystectomy from 37 patients with HIC. Next-generation RNA sequencing demonstrated abundant plasma cell infiltration with frequent light chain restriction in HIC-affected bladder tissue. Subsequent analysis of the B-cell receptor repertoire revealed spatial and temporal expansion of B-cell clones. The extent of B-cell clonal expansion was significantly correlated with the gene expression levels of TNFSF13 and TNFSF13B, which encode APRIL and BAFF, respectively. These findings indicate that APRIL and BAFF are the key regulators of clonal B-cell expansion in HIC and might serve as therapeutic targets in this debilitating disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
The Journal of pathology. 2024 Oct 03 [Epub ahead of print]
Masafumi Horie, Yoshiyuki Akiyama, Hiroto Katoh, Satoru Taguchi, Masaki Nakamura, Keishi Mizuguchi, Yukinobu Ito, Takashi Matsushita, Tetsuo Ushiku, Shumpei Ishikawa, Akiteru Goto, Haruki Kume, Yukio Homma, Daichi Maeda
Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Department of Urology, NTT Medical Center Tokyo, Tokyo, Japan., Department of Diagnostic Pathology, Kanazawa University Hospital, Kanazawa, Japan., Department of Dermatology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan., Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan., Department of Interstitial Cystitis Medicine, Faculty of Medicine, Kyorin University, Tokyo, Japan.