APRIL/BAFF upregulation is associated with clonal B-cell expansion in Hunner-type interstitial cystitis

IF 5.6 2区医学 Q1 ONCOLOGY

The Journal of Pathology Pub Date : 2024-10-03 DOI:10.1002/path.6353

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

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Abstract

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.

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APRIL/BAFF上调与Hunner型间质性膀胱炎的克隆B细胞扩增有关。

亨纳型间质性膀胱炎（HIC）是一种病因不明的膀胱慢性炎症性疾病。我们对 37 名 HIC 患者通过活检和膀胱切除术获得的膀胱标本进行了全面的免疫基因组学分析。新一代 RNA 测序显示，在受 HIC 影响的膀胱组织中，浆细胞大量浸润，轻链频繁受限。随后对 B 细胞受体谱系的分析表明，B 细胞克隆在空间和时间上都发生了扩张。B 细胞克隆扩增的程度与 TNFSF13 和 TNFSF13B（分别编码 APRIL 和 BAFF）的基因表达水平显著相关。这些研究结果表明，APRIL和BAFF是HIC中B细胞克隆扩增的关键调控因子，可能成为这种衰弱性疾病的治疗靶点。© 2024 作者简介病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学会出版。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

The Journal of Pathology 医学-病理学

CiteScore

14.10

自引率

1.40%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.