Characteristics of circulating KSHV-infected viroblasts during active KSHV+ multicentric Castleman disease
© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved..
Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8-associated multicentric Castleman disease (MCD) is a polyclonal B-cell lymphoproliferative disorder that mainly occurs in immunocompromised hosts. The diagnosis relies on lymph node biopsy demonstrating KSHV-infected cells located in the mantle zone with a marked interfollicular plasma cell infiltration. Infected cells are large cells positive for immunoglobulin M (IgM), λ light chain, and CD38, described initially as infected plasmablasts. We show that IgM+λ+CD38high cells were also detectable in the peripheral blood of 14 out of 18 (78%) patients with active KSHV-MCD and absent in 40 controls. Using immunofluorescence and flow-fluorescence in situ hybridization, we demonstrate that these cells are KSHV infected and express both latent and lytic KSHV transcripts. These KSHV-infected viroblasts (KIVs) harbor a distinct phenotype compared with conventional plasmablasts. We also identified several putative mechanisms of immune escape used by KSHV, because KIVs displayed an overall decrease of costimulatory molecules, with a remarkable lack of CD40 expression and are interleukin-10-producing cells. The identification of this specific and easily accessible KSHV+ circulating population brings new elements to the understanding of KSHV-MCD but also raises new questions that need to be clarified.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Blood advances - 7(2023), 9 vom: 09. Mai, Seite 1682-1691 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Martin de Frémont, Gregoire [VerfasserIn] |
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| Links: |
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| Themen: |
Immunoglobulin M |
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| Anmerkungen: |
Date Completed 28.04.2023 Date Revised 15.05.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1182/bloodadvances.2022008456 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350204527 |
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| 520 | |a Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8-associated multicentric Castleman disease (MCD) is a polyclonal B-cell lymphoproliferative disorder that mainly occurs in immunocompromised hosts. The diagnosis relies on lymph node biopsy demonstrating KSHV-infected cells located in the mantle zone with a marked interfollicular plasma cell infiltration. Infected cells are large cells positive for immunoglobulin M (IgM), λ light chain, and CD38, described initially as infected plasmablasts. We show that IgM+λ+CD38high cells were also detectable in the peripheral blood of 14 out of 18 (78%) patients with active KSHV-MCD and absent in 40 controls. Using immunofluorescence and flow-fluorescence in situ hybridization, we demonstrate that these cells are KSHV infected and express both latent and lytic KSHV transcripts. These KSHV-infected viroblasts (KIVs) harbor a distinct phenotype compared with conventional plasmablasts. We also identified several putative mechanisms of immune escape used by KSHV, because KIVs displayed an overall decrease of costimulatory molecules, with a remarkable lack of CD40 expression and are interleukin-10-producing cells. The identification of this specific and easily accessible KSHV+ circulating population brings new elements to the understanding of KSHV-MCD but also raises new questions that need to be clarified | ||
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| 700 | 1 | |a Garzaro, Margaux |e verfasserin |4 aut | |
| 700 | 1 | |a Chbihi, Marwa |e verfasserin |4 aut | |
| 700 | 1 | |a Fournier, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Poirot, Justine |e verfasserin |4 aut | |
| 700 | 1 | |a Dossier, Antoine |e verfasserin |4 aut | |
| 700 | 1 | |a Silvestrini, Marc-Antoine |e verfasserin |4 aut | |
| 700 | 1 | |a Villemonteix, Juliette |e verfasserin |4 aut | |
| 700 | 1 | |a Meignin, Véronique |e verfasserin |4 aut | |
| 700 | 1 | |a Galicier, Lionel |e verfasserin |4 aut | |
| 700 | 1 | |a Bertinchamp, Rémi |e verfasserin |4 aut | |
| 700 | 1 | |a Le Goff, Jerome |e verfasserin |4 aut | |
| 700 | 1 | |a Salmona, Maud |e verfasserin |4 aut | |
| 700 | 1 | |a Flamarion, Edouard |e verfasserin |4 aut | |
| 700 | 1 | |a Cassius, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Lebbé, Celeste |e verfasserin |4 aut | |
| 700 | 1 | |a Ronchetti, Anne Marie |e verfasserin |4 aut | |
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| 700 | 1 | |a Oksenhendler, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Carcelain, Guislaine |e verfasserin |4 aut | |
| 700 | 1 | |a Boutboul, David |e verfasserin |4 aut | |
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