Transcriptome and unique cytokine microenvironment of Castleman disease.
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
31
07
2021
accepted:
05
10
2021
revised:
05
10
2021
pubmed:
24
10
2021
medline:
29
4
2022
entrez:
23
10
2021
Statut:
ppublish
Résumé
Castleman disease (CD) represents a group of rare, heterogeneous and poorly understood disorders that share characteristic histopathological features. Unicentric CD (UCD) typically involves a single enlarged lymph node whereas multicentric CD (MCD) involves multiple lymph node stations. To understand the cellular basis of CD, we undertook a multi-platform analysis using targeted RNA sequencing, RNA in-situ hybridization (ISH), and adaptive immune receptor rearrangements (AIRR) profiling of archived tissue from 26 UCD, 14 MCD, and 31 non-CD reactive controls. UCD showed differential expression and upregulation of follicular dendritic cell markers (CXCL13, clusterin), angiogenesis factors (LPL, DLL4), extracellular matrix remodeling factors (TGFβ, SKIL, LOXL1, IL-1β, ADAM33, CLEC4A), complement components (C3, CR2) and germinal center activation markers (ZDHHC2 and BLK) compared to controls. MCD showed upregulation of IL-6 (IL-6ST, OSMR and LIFR), IL-2, plasma cell differentiation (XBP1), FDC marker (CXCL13, clusterin), fibroblastic reticular cell cytokine (CCL21), angiogenesis factor (VEGF), and mTORC1 pathway genes compared to UCD and controls. ISH studies demonstrated that VEGF was increased in the follicular dendritic cell-predominant atretic follicles and the interfollicular macrophages of MCD compared to UCD and controls. IL-6 expression was higher along interfollicular vasculature-associated cells of MCD. Immune repertoire analysis revealed oligoclonal expansions of T-cell populations in MCD cases (2/6) and UCD cases (1/9) that are consistent with antigen-driven T cell activation. The findings highlight the unique genes, pathways and cell types involved in UCD and MCD. We identify potential novel targets in CD that may be harnessed for therapeutics.
Identifiants
pubmed: 34686774
doi: 10.1038/s41379-021-00950-3
pii: S0893-3952(22)00289-7
pmc: PMC9272352
mid: NIHMS1815112
doi:
Substances chimiques
Clusterin
0
Cytokines
0
Interleukin-6
0
Vascular Endothelial Growth Factor A
0
ADAM Proteins
EC 3.4.24.-
ADAM33 protein, human
EC 3.4.24.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
451-461Subventions
Organisme : NCI NIH HHS
ID : P30 CA016520
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141408
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
Références
Sopfe, J. et al. Castleman disease in pediatrics: Insights on presentation, treatment, and outcomes from a two-site retrospective cohort study. Pediatr. Blood Cancer 66, e27613 (2019).
pubmed: 30680887
pmcid: 6428598
Talat, N., Belgaumkar, A. P. & Schulte, K. M. Surgery in Castleman’s disease: a systematic review of 404 published cases. Ann. Surg. 255, 677–684 (2012).
pubmed: 22367441
Zhang, M. Y. et al. UCD with MCD-like inflammatory state: surgical excision is highly effective. Blood Adv. 5, 122–128 (2021).
pubmed: 33570636
pmcid: 7805307
van Rhee, F. et al. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease. Blood Adv. 4, 6039–6050 (2020).
pubmed: 33284946
pmcid: 7724917
Dispenzieri, A. et al. The clinical spectrum of Castleman’s disease. Am. J. Hematol. 87, 997–1002 (2012).
pubmed: 22791417
pmcid: 3900496
Dispenzieri, A. & Fajgenbaum, D. C. Overview of Castleman disease. Blood 135, 1353–1364 (2020).
pubmed: 32106302
Fajgenbaum, D. C. et al. Insufficient evidence exists to use histopathologic subtype to guide treatment of idiopathic multicentric Castleman disease. Am. J. Hematol. 95, 1553–1561 (2020).
pubmed: 32894785
Fajgenbaum, D. C. et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood 129, 1646–1657 (2017).
pubmed: 28087540
pmcid: 5364342
Fajgenbaum, D. C., Van Rhee, F. & Nabel, C. S. HHV-8-negative, idiopathic multicentric Castleman disease: Novel insights into biology, pathogenesis, and therapy. Blood 123, 2924–2933 (2014).
pubmed: 24622327
Pierson, S. K. et al. Plasma proteomics identifies a ‘chemokine storm’ in idiopathic multicentric Castleman disease. Am. J. Hematol. 93, 902–912 (2018).
pubmed: 29675946
Aoki, Y. et al. Angiogenesis and hematopoiesis induced by Kaposi’s sarcoma-associated herpesvirus-encoded interleukin-6. Blood 93, 4034–4043 (1999).
pubmed: 10361100
Suda, T. et al. HHV-8 infection status of AIDS-unrelated and AIDS-associated multicentric castleman’s disease. Pathol. Int. 51, 671–679 (2001).
pubmed: 11696169
Nishimoto, N. et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 106, 2627–2632 (2005).
pubmed: 15998837
van Rhee, F. et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 15, 966–974, https://doi.org/10.1016/S1470-2045(14)70319-5 (2014).
doi: 10.1016/S1470-2045(14)70319-5
pubmed: 25042199
Nishi, J. et al. Expression of vascular endothelial growth factor in sera and lymph nodes of the plasma cell type of Castleman’s disease. Br. J. Haematol. 104, 482–485 (1999).
pubmed: 10086783
Chen, W. C. et al. Cytogenetic anomalies in hyaline vascular Castleman disease: Report of two cases with reappraisal of histogenesis. Cancer Genet. Cytogenet. 164, 110–117 (2006).
pubmed: 16434312
Radaszkiewicz, T., Lennert, K. & Hansmann, M.-L. Monoclonality and polyclonality of plasma cells in Castleman’s disease of the plasma cell variant. Histopathology 14, 11–24, https://doi.org/10.1111/j.1365-2559.1989.tb02110.x (1989).
doi: 10.1111/j.1365-2559.1989.tb02110.x
pubmed: 2925176
Wang, H. W., Pittaluga, S. & Jaffe, E. S. Multicentric Castleman disease: Where are we now? Semin. Diagnostic Pathol. 33, 294–306 (2016).
Chang, K. C. et al. Monoclonality and cytogenetic abnormalities in hyaline vascular Castleman disease. Mod. Pathol. 27, 823–831 (2014).
pubmed: 24201121
Baker, T. S. et al. A novel FAS mutation with variable expressivity in a family with unicentric and idiopathic multicentric Castleman disease. Blood Adv. 2, 2959–2963 (2018).
pubmed: 30404775
pmcid: 6234382
Nagy, A. et al. Next-generation sequencing of idiopathic multicentric and unicentric Castleman disease and follicular dendritic cell sarcomas. Blood Adv. 2, 481–491 (2018).
pubmed: 29496669
pmcid: 5851414
Endo, Y. et al. Mediterranean fever gene variants modify clinical phenotypes of idiopathic multi-centric Castleman disease. Clin. Exp. Immunol. 206, 91–98, https://doi.org/10.1111/cei.13632 (2021).
doi: 10.1111/cei.13632
pubmed: 34096620
pmcid: 8663796
You, L. et al. Whole-exome sequencing identifies novel somatic alterations associated with outcomes in idiopathic multicentric Castleman disease. Br. J. Haematol. 188, e64–e67 (2020).
pubmed: 31863597
Li, Z. et al. Recurrent PDGFRB mutations in unicentric Castleman disease. Leukemia 33, 1035–1038 (2019).
pubmed: 30607019
pmcid: 6484698
Qi, Z. et al. Reliable gene expression profiling from small and hematoxylin and eosin-stained clinical formalin-fixed, paraffin-embedded specimens using the HTG EdgeSeq platform. J. Mol. Diagn. 21, 796–807 (2019).
pubmed: 31255795
Godoy, P. M. et al. Comparison of reproducibility, accuracy, sensitivity, and specificity of miRNA quantification platforms. Cell Rep. 29, 4212–4222.e4215 (2019).
pubmed: 31851944
pmcid: 7499898
Zhang, L. et al. Cross-platform comparison of immune-related gene expression to assess intratumor immune responses following cancer immunotherapy. J. Immunol. Methods 494, 113041 (2021).
pubmed: 33753096
Wang, L. et al. EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer. Nat. Commu.n 9, 3503 (2018).
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
pubmed: 25605792
pmcid: 4402510
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).
pubmed: 30944313
pmcid: 6447622
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
pubmed: 16199517
pmcid: 1239896
Szklarczyk, D. et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43, D447–D452 (2015).
pubmed: 25352553
Bader, G. D. & Hogue, C. W. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform. 4, 2 (2003).
Leick, M. et al. T cell clonal dynamics determined by high-resolution tcr-Beta sequencing in recipients after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 26, 1567–1574 (2020).
Meng, W. et al. An atlas of B-cell clonal distribution in the human body. Nat. Biotechnol. 35, 879–884 (2017).
pubmed: 28829438
pmcid: 5679700
Miron, M., et al. Human lymph nodes maintain quiescent memory T cells with high functional potential and clonal diversity throughout life. J. Immunol. 201, 2132–2140 (2021).
Rosenfeld, A. M., Meng, W., Luning Prak, E. T. & Hershberg, U. ImmuneDB, a novel tool for the analysis, storage, and dissemination of immune repertoire sequencing data. Front. Immunol. 9, 2107 (2018).
pubmed: 30298069
pmcid: 6161679
Miron, M. et al. Maintenance of the human memory T cell repertoire by subset and tissue site. Genome Med. 13, 100 (2021).
pubmed: 34127056
pmcid: 8204429
Ye, J., Ma, N., Madden, T. L. & Ostell, J. M. IgBLAST: an immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res. 41, W34–W40 (2013).
pubmed: 23671333
pmcid: 3692102
Kuri-Cervantes, L. et al. Comprehensive mapping of immune perturbations associated with severe COVID-19. Sci. Immunol. 5, (49) (2020).
Oksenhendler, E. et al. The full spectrum of Castleman disease: 273 patients studied over 20 years. Br. J. Haematol. 180, 206–216 (2018).
pubmed: 29143319
Chisholm, K. M. & Fleming, M. D. Histologic and laboratory characteristics of symptomatic and asymptomatic Castleman disease in the pediatric population. Am. J. Clin. Pathol. 153, 821–832 (2020).
pubmed: 32112075
pmcid: 7453143
Nishi, J. I. & Maruyama, I. Increased expression of vascular endothelial growth factor (VEGF) in Castleman’s disease: proposed pathomechanism of vascular proliferation in the affected lymph node. Leuk. Lymphoma 38, 387–394 (2000).
pubmed: 10830746
Arenas, D. J. et al. Increased mTOR activation in idiopathic multicentric Castleman disease. Blood 135, 1673–1684 (2020). May 7(2020-1684).
pubmed: 32206779
pmcid: 7205815
Baker, T. S. et al. A novel. Blood Adv. 2, 2959–2963 (2018).
pubmed: 30404775
pmcid: 6234382
Leger-Ravet, M. B. et al. Interleukin-6 gene expression in Castleman’s disease. Blood 78, 2923–2930 (1991).
pubmed: 1954381
Yoshizaki, K. et al. Pathogenic Significance of Interleukin-6 (IL-6/BSF-2) in Castleman’s Disease. Blood 74, 1360–1367 (1989).
pubmed: 2788466
Ishiyama, T. et al. Immunodeficiency and IL‐6 production by peripheral blood monocytes in multicentric Castleman’s disease. Br. J. Haematol. 86, 483–489 (1994).
pubmed: 8043430
Lai, Y.-m et al. Expression of interleukin-6 and its clinicopathological significance in Castleman’s disease. Chin. J. Hematol. 34, 404–408 (2013).
Post, G. R. et al. Diagnostic utility of interleukin-6 expression by immunohistochemistry in differentiating castleman disease subtypes and reactive lymphadenopathies. Ann. Clin. Lab. Sci. 46, 474–479 (2016).
pubmed: 27650613
Jourdan, M. et al. IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors. Leukemia 28, 1647–1656 (2014).
pubmed: 24504026
Lin, O. & Frizzera, G. Angiomyoid and follicular dendritic cell proliferative lesions in Castleman’s disease of hyaline-vascular type: a study of 10 cases. Am. J. Surg. Pathol. 21, 1295–1306, https://doi.org/10.1097/00000478-199711000-00004 (1997).
doi: 10.1097/00000478-199711000-00004
pubmed: 9351567
Fajgenbaum, D., Rosenbach, M., Van Rhee, F., Nasir, A. & Reutter, J. Eruptive cherry hemangiomatosis associated with multicentric Castleman disease: a case report and diagnostic clue. JAMA Dermatol. 149, 204–208 (2013).
pubmed: 23426475
van Rhee, F. et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood 132, 2115–2124 (2018).
pubmed: 30181172
pmcid: 6238190
Pai, R. L., et al. Type I IFN response associated with mTOR activation in the TAFRO subtype of idiopathic multicentric Castleman disease. JCI Insight 5, May 7;5:e135031 (2020).
Ohyashiki, J. H. et al. Molecular genetic, cytogenetic, and immunophenotypic analyses in Castleman’s disease of the plasma cell type. Am. J. Clin. Pathol. 101, 290–295, https://doi.org/10.1093/ajcp/101.3.290 (1994).
doi: 10.1093/ajcp/101.3.290
pubmed: 8135184
Kussick, S. J., Kalnoski, M., Braziel, R. M. & Wood, B. L. Prominent clonal B-cell populations identified by flow cytometry in histologically reactive lymphoid proliferations. Am. J. Clin. Pathol. 121, 464–472 (2004).
pubmed: 15080297