{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:39:31Z","timestamp":1792687171101,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute","award":["K08HL171943"],"award-info":[{"award-number":["K08HL171943"]}]},{"name":"U.S. Food and Drug Administration","award":["R01FD007632"],"award-info":[{"award-number":["R01FD007632"]}]},{"name":"National Center Advancing Translational Sciences","award":["KL2TR001879"],"award-info":[{"award-number":["KL2TR001879"]}]},{"name":"Doris Duke Charitable Foundation","award":["Physician Scientist Fellowship"],"award-info":[{"award-number":["Physician Scientist Fellowship"]}]},{"name":"American Society of Hematology","award":["Scholar Award"],"award-info":[{"award-number":["Scholar Award"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["R01AI091627"],"award-info":[{"award-number":["R01AI091627"]}]},{"name":"National Cancer Institute","award":["R01CA278976"],"award-info":[{"award-number":["R01CA278976"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Castleman disease (CD) is an inflammatory disorder characterized by lymphadenopathy with distinctive histologic features, yet its pathophysiology remains poorly understood. This delays diagnoses and limits treatments, leading to additional morbidity and mortality. We used single- cell and spatial transcriptomics to characterize lymph nodes from unicentric CD (UCD) compared with non-specific inflammatory lymphadenopathies. While hematopoietic cells showed few compositional or transcriptional differences, lymph node stromal cells exhibited marked alterations in UCD, most notably an increased abundance of vascular smooth muscle cells (VSMCs) and broadly increased stromal signaling activity. A generalized linear model distinguished histologically indeterminate lymph nodes resembling UCD from non-specific inflammation most accurately using stromal rather than hematopoietic cell composition. Immunohistochemical staining for the VSMC marker CD146 (Melanoma Cell Adhesion Molecule, MCAM) further discriminated UCD from other causes of lymphadenopathy. Together, these findings identify increased VSMC abundance as a hallmark of UCD and suggest that this stromal signature can be leveraged to improve pathologic diagnosis and patient stratification.<\/jats:p>","DOI":"10.1172\/jci.insight.203223","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:27Z","timestamp":1792684827000},"source":"Crossref","is-referenced-by-count":0,"title":["Vascular smooth muscle cell abundance is a hallmark of Castleman Disease"],"prefix":"10.1172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0652-5791","authenticated-orcid":true,"given":"Joshua D.","family":"Brandstadter","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Meili","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Zinski","sequence":"additional","affiliation":[{"name":"Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Wei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"Laczko","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-475X","authenticated-orcid":true,"given":"Michael 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Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Stanossek","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Onder","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mechthild","family":"L\u03cbtge","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"De Martin","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, 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America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7126-6226","authenticated-orcid":true,"given":"Vinodh","family":"Pillai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon C.","family":"Aster","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Nasta","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Ludewig","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7367-8184","authenticated-orcid":true,"given":"David C.","family":"Fajgenbaum","sequence":"additional","affiliation":[{"name":"Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of 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