Advertisement

ResearchIn-Press PreviewHematologyImmunologyInflammation Open Access | 10.1172/jci.insight.203223

Vascular smooth muscle cell abundance is a hallmark of Castleman Disease

Joshua D. Brandstadter,1 Samuel Meili,2 Joseph Zinski,3 Hung-Wei Cheng,2 Dorottya Laczko,4 Michael V. Gonzalez,3 Subin S. George,5 Megan S Lim,6 Adam Bagg,4 Yves Stanossek,2 Lucas Onder,2 Mechthild Lϋtge,2 Angelina De Martin,2 Bridget Austin,3 Melanie Mumau,3 Katherine S. Forsyth,3 Vinodh Pillai,4 Antonio Ferreira,7 Jon C. Aster,7 Sunita Nasta,1 Burkhard Ludewig,2 David C. Fajgenbaum,3 and Ivan Maillard1

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Brandstadter, J. in: PubMed | Google Scholar |

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Meili, S. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Zinski, J. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Cheng, H. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Laczko, D. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Gonzalez, M. in: PubMed | Google Scholar |

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by George, S. in: PubMed | Google Scholar |

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Lim, M. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Bagg, A. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Stanossek, Y. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Onder, L. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Lϋtge, M. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by De Martin, A. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Austin, B. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Mumau, M. in: PubMed | Google Scholar |

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Forsyth, K. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Pillai, V. in: PubMed | Google Scholar |

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Ferreira, A. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Aster, J. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Nasta, S. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Ludewig, B. in: PubMed | Google Scholar

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Fajgenbaum, D. in: PubMed | Google Scholar |

1Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

2Institute of Immunobiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3Center for Cytokine Storm Treatment & Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

5Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

6Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, United States of America

7Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States of America

Find articles by Maillard, I. in: PubMed | Google Scholar |

Published October 22, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.203223.
Copyright © 2026, Brandstadter et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 22, 2026 - Version history
View PDF
Abstract

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.

Supplemental material

View

Version history
  • Version 1 (October 22, 2026): In-Press Preview
Advertisement
Advertisement