{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:08:07Z","timestamp":1784308087936,"version":"3.55.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81130030"],"award-info":[{"award-number":["81130030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81000694"],"award-info":[{"award-number":["81000694"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82504275"],"award-info":[{"award-number":["82504275"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Rising Star Program Sailing Project","award":["24YF2738200"],"award-info":[{"award-number":["24YF2738200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Unicentric Castleman disease (UCD), a rare lymphoproliferative disorder, is frequently complicated by paraneoplastic pemphigus (PNP), an autoimmune mucocutaneous syndrome with high mortality. The hyaline\u2013vascular (HV) histological subtype predominates in UCD-PNP, yet the mechanisms driving vascular hyalinization and stromal dysregulation remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To elucidate the cellular and molecular pathogenesis of UCD-PNP through integrated transcriptomic and cellular analyses, focusing on stromal\u2013immune crosstalk and mechanisms underlying extracellular matrix (ECM) dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed bulk RNA sequencing (RNAseq) of lymph node samples from 33 patients with pathologically confirmed UCD-PNP and single-cell RNAseq (scRNAseq) in 5 of them. Analytical approaches included differential expression, pathway enrichment, cellular deconvolution, developmental trajectory inference, ligand\u2013receptor interaction analysis and spatial validation. The functional consequences of identified interactions were assessed using bulk RNAseq and proteomic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bulk RNAseq highlighted ECM dysregulation, with significant upregulation of collagen genes in UCD-PNP. scRNAseq of 58 811 cells revealed expansion of endothelial cells (ECs), pericytes and fibroblasts, alongside diminished follicular dendritic cells (FDCs). Cell\u2013cell communication analysis identified ECs as primary contributors to collagen and laminin overproduction via COL4A1\u2013ITGA1\/ITGB1 and LAMB1\u2013ITGA6\/ITGB1 signalling, directly linking EC activity to perivascular hyalinization. UCD-PNP also featured marked plasmablast expansion, IgG class-switching and memory CD4+ T cells driving B-cell hyperactivity. In addition, ligand\u2013receptor analysis revealed a pivotal interaction between EC-derived COL4A1 and CD44 on B cells. Mechanistically, COL4A1 overexpression in ECs upregulated genes involved in ECM organization and remodelling. Furthermore, proteomics revealed EC\u2013B-cell crosstalk-derived vascular basement membrane accumulation (perlecan, encoded by HSPG2) and proinflammatory cytokine release (CCL4) in functional co-cultures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>UCD-PNP pathogenesis centres on aberrant EC expansion and dysregulation, driving simultaneous vascular hyalinization via excessive ECM deposition. Pathological EC\u2013B-cell interactions directly link basement membrane accumulation to proinflammatory signalling. Targeting this EC-driven stromal\u2013immune crosstalk presents a novel therapeutic strategy for UCD-PNP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljag153","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T11:13:53Z","timestamp":1776510833000},"page":"304-315","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptome profiling reveals that cellular composition contributes to the hyaline-vascular variant in unicentric Castleman disease-associated paraneoplastic pemphigus"],"prefix":"10.1093","volume":"195","author":[{"given":"Sai","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"National Clinical Research Center for Skin and Sexually Transmitted Diseases , Beijing ,","place":["China"]},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses , Beijing ,","place":["China"]},{"name":"National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"National Clinical Research Center for Skin and Sexually Transmitted Diseases , Beijing ,","place":["China"]},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses , Beijing ,","place":["China"]},{"name":"National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinmo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking University First Hospital , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"National Clinical Research Center for Skin and Sexually Transmitted Diseases , Beijing ,","place":["China"]},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses , Beijing ,","place":["China"]},{"name":"National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixue","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"National Clinical Research Center for Skin and Sexually Transmitted Diseases , Beijing ,","place":["China"]},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses , Beijing ,","place":["China"]},{"name":"National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"National Clinical Research Center for Skin and Sexually Transmitted Diseases , Beijing ,","place":["China"]},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses , Beijing ,","place":["China"]},{"name":"National Medical Products Administration Key Laboratory for Quality 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Venereology, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"National Clinical Research Center for Skin and Sexually Transmitted Diseases , Beijing ,","place":["China"]},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses , Beijing ,","place":["China"]},{"name":"National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics , Beijing ,","place":["China"]},{"name":"Department of Pathology, Shantou University Medical College , Shantou, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8317-3414","authenticated-orcid":false,"given":"Mingyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"National Clinical Research Center for Skin and Sexually Transmitted Diseases , Beijing ,","place":["China"]},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses , Beijing ,","place":["China"]},{"name":"National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"2026071712534942100_ljag153-B1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/1097-0142(195607\/08)9:4<822::AID-CNCR2820090430>3.0.CO;2-4","article-title":"Localized mediastinal lymphnode hyperplasia resembling thymoma","volume":"9","author":"Castleman","year":"1956","journal-title":"Cancer"},{"key":"2026071712534942100_ljag153-B2","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1182\/blood.2019000931","article-title":"Overview of Castleman 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