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We conducted comprehensive immunogenomic profiling of bladder specimens obtained by biopsy and cystectomy from 37 patients with HIC. Next\u2010generation RNA sequencing demonstrated abundant plasma cell infiltration with frequent light chain restriction in HIC\u2010affected bladder tissue. Subsequent analysis of the B\u2010cell receptor repertoire revealed spatial and temporal expansion of B\u2010cell clones. The extent of B\u2010cell clonal expansion was significantly correlated with the gene expression levels of\n                    <jats:italic>TNFSF13<\/jats:italic>\n                    and\n                    <jats:italic>TNFSF13B<\/jats:italic>\n                    , which encode APRIL and BAFF, respectively. These findings indicate that APRIL and BAFF are the key regulators of clonal B\u2010cell expansion in HIC and might serve as therapeutic targets in this debilitating disease. \u00a9 2024 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6353","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T04:35:02Z","timestamp":1727930102000},"page":"383-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["<scp>APRIL<\/scp>\n                    \/\n                    <scp>BAFF<\/scp>\n                    upregulation is associated with clonal B\u2010cell expansion in Hunner\u2010type interstitial cystitis"],"prefix":"10.1002","volume":"264","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-4077","authenticated-orcid":false,"given":"Masafumi","family":"Horie","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"},{"name":"Department of Urology Shinshu University School of Medicine  Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9440-728X","authenticated-orcid":false,"given":"Hiroto","family":"Katoh","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Graduate School of Medicine The University of Tokyo  Tokyo 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