Interleukin‐6 transcripts up‐regulation in lymph nodes from unicentric and multicentric Castleman disease
Abstract Introduction Castleman disease (CD) represents a spectrum of heterogeneous lymphoproliferative disorders sharing peculiar histopathological features, clinically subdivided into unicentric CD (UCD) and multicentric CD (MCD) and presenting with variable inflammatory symptoms. Interleukin (IL)...
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Wiley
2024-12-01
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| Online Access: | https://doi.org/10.1002/jha2.1034 |
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| author | Marco Lucioni Gaia Morello Caterina Cristinelli Sara Fraticelli Giuseppe Neri Erica Travaglino Marco Minetto Francesca Antoci Paolo Libretti Marcello Gambacorta Luca Arcaini Claudio Tripodo Marco Paulli |
| author_facet | Marco Lucioni Gaia Morello Caterina Cristinelli Sara Fraticelli Giuseppe Neri Erica Travaglino Marco Minetto Francesca Antoci Paolo Libretti Marcello Gambacorta Luca Arcaini Claudio Tripodo Marco Paulli |
| author_sort | Marco Lucioni |
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| description | Abstract Introduction Castleman disease (CD) represents a spectrum of heterogeneous lymphoproliferative disorders sharing peculiar histopathological features, clinically subdivided into unicentric CD (UCD) and multicentric CD (MCD) and presenting with variable inflammatory symptoms. Interleukin (IL)‐6 and other cytokines play a major role in mediating CD inflammatory manifestations. Although the local microenvironment seems to be among the major sources of hypercytokinemia, the precise cellular origin of IL‐6 production in CD is still debated. Methods A series of five nodal CD of different subtypes (one UCD, two idiopathic MCDs [iMCDs], one HIV‐negative human herpesvirus 8 (HHV8)‐associated MCD, and one HIV‐positive HHV8‐associated MCD) and a non‐CD reactive control were tested using RNAscope analysis and a dual in situ hybridization (ISH)/immunohistochemistry technique, in order to quantify IL‐6 expression and its spatial distribution. Quantitative analyses of in situ mRNA were performed on digitalized slides using the HISTOQUANT software (3DHISTECH) and differences between cases were evaluated by the Kruskal‐Wallis test. Results RNA‐ISH documented increased IL‐6 expression in all CD lymph nodes, independently from clinical and pathological subtypes, however, the highest levels were found in HHV8+ cases and statistically significant differences in IL‐6 expression were found only between HHV8+ MCD and control case. Dual RNA‐ISH for IL6 coupled with immunohistochemistry analysis showed that IL‐6 was overexpressed in CD31‐positive endothelial cells in 5/5 CD tested cases but not in the control case. Conclusion Our findings suggest that nodal IL‐6 expression seems to be significantly upregulated in HHV8+ MCD, but a trend toward increased nodal IL‐6 expression was noticed also in UCD and iMCD‐not otherwise specified. CD31+ endothelial cells probably represent one of the major sources of IL‐6 production in the nodal microenvironment. |
| format | Article |
| id | doaj-art-9df71f47d78f44859b6f62ab80a193a4 |
| institution | DOAJ |
| issn | 2688-6146 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
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| spelling | doaj-art-9df71f47d78f44859b6f62ab80a193a42025-08-20T02:49:17ZengWileyeJHaem2688-61462024-12-01561182118910.1002/jha2.1034Interleukin‐6 transcripts up‐regulation in lymph nodes from unicentric and multicentric Castleman diseaseMarco Lucioni0Gaia Morello1Caterina Cristinelli2Sara Fraticelli3Giuseppe Neri4Erica Travaglino5Marco Minetto6Francesca Antoci7Paolo Libretti8Marcello Gambacorta9Luca Arcaini10Claudio Tripodo11Marco Paulli12Department of Molecular Medicine University of Pavia Pavia ItalyDepartment of Sciences for Health Promotion and Mother‐Child Care “G.D'Alessandro” Tumor Immunology Unit University of Palermo Palermo ItalyDepartment of Molecular Medicine University of Pavia Pavia ItalyDepartment of Molecular Medicine University of Pavia Pavia ItalyDepartment of Molecular Medicine University of Pavia Pavia ItalyPathology Unit, Fondazione IRCCS Policlinico “San Matteo” Pavia ItalyDepartment of Molecular Medicine University of Pavia Pavia ItalyPathology Unit, Fondazione IRCCS Policlinico “San Matteo” Pavia ItalySynLab Italia Srl Castenedolo ItalyIRCCS SynLab SDN Naples ItalyDepartment of Molecular Medicine University of Pavia Pavia ItalyDepartment of Sciences for Health Promotion and Mother‐Child Care “G.D'Alessandro” Tumor Immunology Unit University of Palermo Palermo ItalyDepartment of Molecular Medicine University of Pavia Pavia ItalyAbstract Introduction Castleman disease (CD) represents a spectrum of heterogeneous lymphoproliferative disorders sharing peculiar histopathological features, clinically subdivided into unicentric CD (UCD) and multicentric CD (MCD) and presenting with variable inflammatory symptoms. Interleukin (IL)‐6 and other cytokines play a major role in mediating CD inflammatory manifestations. Although the local microenvironment seems to be among the major sources of hypercytokinemia, the precise cellular origin of IL‐6 production in CD is still debated. Methods A series of five nodal CD of different subtypes (one UCD, two idiopathic MCDs [iMCDs], one HIV‐negative human herpesvirus 8 (HHV8)‐associated MCD, and one HIV‐positive HHV8‐associated MCD) and a non‐CD reactive control were tested using RNAscope analysis and a dual in situ hybridization (ISH)/immunohistochemistry technique, in order to quantify IL‐6 expression and its spatial distribution. Quantitative analyses of in situ mRNA were performed on digitalized slides using the HISTOQUANT software (3DHISTECH) and differences between cases were evaluated by the Kruskal‐Wallis test. Results RNA‐ISH documented increased IL‐6 expression in all CD lymph nodes, independently from clinical and pathological subtypes, however, the highest levels were found in HHV8+ cases and statistically significant differences in IL‐6 expression were found only between HHV8+ MCD and control case. Dual RNA‐ISH for IL6 coupled with immunohistochemistry analysis showed that IL‐6 was overexpressed in CD31‐positive endothelial cells in 5/5 CD tested cases but not in the control case. Conclusion Our findings suggest that nodal IL‐6 expression seems to be significantly upregulated in HHV8+ MCD, but a trend toward increased nodal IL‐6 expression was noticed also in UCD and iMCD‐not otherwise specified. CD31+ endothelial cells probably represent one of the major sources of IL‐6 production in the nodal microenvironment.https://doi.org/10.1002/jha2.1034HHV8IL‐6 transcriptsmulticentric Castleman diseaseRNA‐ISHunicentric Castleman disease |
| spellingShingle | Marco Lucioni Gaia Morello Caterina Cristinelli Sara Fraticelli Giuseppe Neri Erica Travaglino Marco Minetto Francesca Antoci Paolo Libretti Marcello Gambacorta Luca Arcaini Claudio Tripodo Marco Paulli Interleukin‐6 transcripts up‐regulation in lymph nodes from unicentric and multicentric Castleman disease eJHaem HHV8 IL‐6 transcripts multicentric Castleman disease RNA‐ISH unicentric Castleman disease |
| title | Interleukin‐6 transcripts up‐regulation in lymph nodes from unicentric and multicentric Castleman disease |
| title_full | Interleukin‐6 transcripts up‐regulation in lymph nodes from unicentric and multicentric Castleman disease |
| title_fullStr | Interleukin‐6 transcripts up‐regulation in lymph nodes from unicentric and multicentric Castleman disease |
| title_full_unstemmed | Interleukin‐6 transcripts up‐regulation in lymph nodes from unicentric and multicentric Castleman disease |
| title_short | Interleukin‐6 transcripts up‐regulation in lymph nodes from unicentric and multicentric Castleman disease |
| title_sort | interleukin 6 transcripts up regulation in lymph nodes from unicentric and multicentric castleman disease |
| topic | HHV8 IL‐6 transcripts multicentric Castleman disease RNA‐ISH unicentric Castleman disease |
| url | https://doi.org/10.1002/jha2.1034 |
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