scholarly journals How I treat HHV8/KSHV-related diseases in posttransplant patients

Blood ◽  
2012 ◽  
Vol 120 (20) ◽  
pp. 4150-4159 ◽  
Author(s):  
Giovanni Riva ◽  
Mario Luppi ◽  
Patrizia Barozzi ◽  
Fabio Forghieri ◽  
Leonardo Potenza
Keyword(s):  
Primary Effusion Lymphoma ◽  
Bone Marrow Failure ◽  
Clinical Manifestations ◽  
Human Herpesvirus ◽  
Calcineurin Inhibitors ◽  
Kaposi Sarcoma ◽  
Mtor Inhibitors ◽  
Castleman Disease ◽  
Diagnostic Features ◽  
Multicentric Castleman Disease

Abstract Posttransplantation human herpesvirus-8 (HHV8)/Kaposi sarcoma herpesvirus (KSHV) primary infection and/or reactivations are associated with uncommon and sometimes fatal, neoplastic, and non-neoplastic diseases. HHV8-related clinical manifestations notably range from Kaposi sarcoma (KS) to either primary effusion lymphoma or multicentric Castleman disease B-cell malignancies, and from polyclonal HHV8-positive plasmacytic lymphoproliferative disorders to bone marrow failure and peripheral cytopenias, associated or not with hemophagocytic syndromes, and to acute hepatitis syndromes. We reviewed the patient series reported in the literature and summarized clinical management aspects, in terms of diagnosis, follow-up, and treatment. We described typical clinical presentations and histopathologic diagnostic features of these diseases, and we discussed the role of HHV8-specific serologic, molecular, and immunologic assays, particularly focusing on recent data from HHV8-specific T-cell monitoring in posttransplantation KS patients. We finally discussed actual therapeutic options, namely, the reduction or discontinuation of immunosuppressive therapy or the switch from calcineurin inhibitors to mTOR inhibitors, as alternatives to antineoplastic chemotherapy, along with the use of antiherpesvirus agents as prophylactic or therapeutic measures, and treatment with rituximab in posttrans-plantation multicentric Castleman disease patients and non-neoplastic HHV8-associated syndromes.

scholarly journals Update on Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) – review

2020 ◽  
Vol 58 (4) ◽  
pp. 199-208
Author(s):  
Nicoleta Iftode ◽  
Mihaela Andreea Rădulescu ◽  
Ștefan Sorin Aramă ◽  
Victoria Aramă
Keyword(s):  
Current Knowledge ◽  
Primary Effusion Lymphoma ◽  
Clinical Manifestations ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Diagnosis And Treatment ◽  
Herpesvirus 8 ◽  
Kshv Infection ◽  
Multicentric Castleman Disease

AbstractHuman herpesvirus 8 (HHV8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), is one of the few pathogens recognized as direct carcinogen, being involved in the pathogenesis of Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease. KSHV is a relatively recently discovered virus, with still limited possibilities for diagnosis and treatment. Therefore, ongoing studies are trying to answer the main issues related to the management of KSHV infection and its associated diseases. This review updates the current knowledge of the KSHV infection, discussing aspects related to epidemiology, virological features, clinical manifestations, diagnosis and treatment.

scholarly journals Kaposi sarcoma–associated herpesvirus/human herpesvirus 8–associated lymphoproliferative disorders

Blood ◽  
2019 ◽  
Vol 133 (11) ◽  
pp. 1186-1190 ◽  
Author(s):  
Eric Oksenhendler ◽  
David Boutboul ◽  
Lionel Galicier
Keyword(s):  
B Cells ◽  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Lymphoproliferative Disorders ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8 ◽  
Multicentric Castleman Disease ◽  
Infected Cells

Abstract Kaposi sarcoma–associated herpesvirus/human herpesvirus 8 is associated with multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). In MCD, infected B cells, although polyclonal, express a monotypic immunoglobulin Mλ phenotype, probably through editing toward λ light chain in mature B cells. They are considered to originate from pre–germinal center (GC) naive B cells. Both viral and human interleukin-6 contribute to the plasmacytic differentiation of these cells, and viral replication can be observed in some infected cells. PEL cells are clonal B cells considered as GC/post-GC B cells. One can also hypothesize that they originate from the same infected naive B cells and that additional factors could be responsible for their peculiar phenotype.

Human herpesvirus-8: Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Lawrence D. Kaplan
Keyword(s):  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8 ◽  
Multicentric Castleman Disease ◽  
Cell Cycle Entry ◽  
Clinical Challenge ◽  
Gamma Herpesvirus

Abstract Human herpesvirus 8 (HHV8) is a gamma herpesvirus associated with Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma, lymphoproliferative diseases that are most commonly observed in immunocompromised individuals. The viral genome expresses genes responsible for inhibition of apoptosis, cell cycle entry, and angiogenesis. Viral homologs of human regulatory genes are expressed, providing stimuli for angiogenesis, B-cell proliferation, and immune evasion. Variations in expression of these factors give rise to the 3 known HHV8-associated malignancies. Identification of these pathogenetic mechanisms has led to exploration of targeted treatment approaches for all 3 of these disorders with success in Kaposi sarcoma and multicentric Castleman disease; primary effusion lymphoma remains a clinical challenge.

High incidence of Kaposi sarcoma–associated herpesvirus–related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease

Blood ◽  
2002 ◽  
Vol 99 (7) ◽  
pp. 2331-2336 ◽  
Author(s):  
Eric Oksenhendler ◽  
Emmanuelle Boulanger ◽  
Lionel Galicier ◽  
Ming-Qing Du ◽  
Nicolas Dupin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Hiv Infection ◽  
Hodgkin Lymphoma ◽  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Herpesvirus Type ◽  
Multicentric Castleman Disease ◽  
Non Hodgkin Lymphoma

Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin 6 (IL-6) dysregulation. In the context of human immunodeficiency virus (HIV) infection, MCD is associated with Kaposi sarcoma–associated herpesvirus, also called human herpesvirus type 8 (KSHV/HHV8). Within a prospective cohort study on 60 HIV-infected patients with MCD, and a median follow-up period of 20 months, 14 patients developed KSHV/HHV8-associated non-Hodgkin lymphoma (NHL): 3 “classic” KSHV/HHV8+ Epstein-Barr virus–positive (EBV+) primary effusion lymphoma (PEL), 5 KSHV/HHV8+ EBV− visceral large cell NHL with a PEL-like phenotype, and 6 plasmablastic lymphoma/leukemia (3/3 KSHV/HHV8+ EBV−). The NHL incidence observed in this cohort study (101/1000 patient-years) is about 15-fold what is expected in the general HIV+ population. MCD-associated KSHV/HHV8+ NHL fell into 2 groups, suggesting different pathogenesis. The plasmablastic NHL likely represents the expansion of plasmablastic microlymphoma from the MCD lesion and progression toward aggressive NHL. In contrast, the PEL and PEL-like NHL may implicate a different original infected cell whose growth is promoted by the cytokine-rich environment of the MCD lesions.

scholarly journals KSHV- and EBV-associated germinotropic lymphoproliferative disorder

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3415-3418 ◽  
Author(s):  
Ming-Qing Du ◽  
Tim C. Diss ◽  
Hongxiang Liu ◽  
Hongtao Ye ◽  
Rifat A. Hamoudi ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Gene Rearrangement ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Lymphoproliferative Disorders ◽  
Multicentric Castleman Disease ◽  
Tissue Sections ◽  
Response To Chemotherapy ◽  
Ig Heavy Chain

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic κ or λ light chain. Clusters of CD10+CD20+ residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity “KSHV-associated germinotropic lymphoproliferative disorder.”

scholarly journals Latent KSHV infection increases the vascular permeability of human endothelial cells

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5344-5354 ◽  
Author(s):  
Christophe Guilluy ◽  
Zhigang Zhang ◽  
Prasanna M. Bhende ◽  
Lisa Sharek ◽  
Ling Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Permeability ◽  
Latent Infection ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Cell Junctions ◽  
Paracrine Factors ◽  
Kshv Infection ◽  
Multicentric Castleman Disease

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is associated with 3 different human malignancies: Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. The KS lesion is driven by KSHV-infected endothelial cells and is highly dependent on autocrine and paracrine factors for survival and growth. We report that latent KSHV infection increases the vascular permeability of endothelial cells. Endothelial cells with latent KSHV infection display increased Rac1 activation and activation of its downstream modulator, p21-activated kinase 1 (PAK1). The KSHV-infected cells also exhibit increases in tyrosine phosphorylation of vascular endothelial (VE)–cadherin and β-catenin, whereas total levels of these proteins remained unchanged, suggesting that latent infection disrupted endothelial cell junctions. Consistent with these findings, we found that KSHV-infected endothelial cells displayed increased permeability compared with uninfected endothelial cells. Knockdown of Rac1 and inhibition of reactive oxygen species (ROS) resulted in decreased permeability in the KSHV-infected endothelial cells. We further demonstrate that the KSHV K1 protein can activate Rac1. Rac1 was also highly activated in KSHV-infected endothelial cells and KS tumors. In conclusion, KSHV latent infection increases Rac1 and PAK1 activity in endothelial cells, resulting in the phosphorylation of VE-cadherin and β-catenin and leading to the disassembly of cell junctions and to increased vascular permeability of the infected endothelial cells.

Molecular evidence of organ-related transmission of Kaposi sarcoma–associated herpesvirus or human herpesvirus-8 in transplant patients

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3279-3281
Author(s):  
Mario Luppi ◽  
Patrizia Barozzi ◽  
Gaia Santagostino ◽  
Raffaella Trovato ◽  
Thomas F. Schulz ◽  
...  
Keyword(s):  
Genetic Relatedness ◽  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Human Herpesvirus 8 ◽  
Molecular Evidence ◽  
Herpesvirus 8 ◽  
Transplant Patients ◽  
High Level

In transplant patients, Kaposi sarcoma (KS)-associated herpesvirus or human herpesvirus-8 (HHV-8) infection is associated with the development of KS, primary effusion lymphoma and Castleman disease. Whether HHV-8 is either reactivated in the recipient or transmitted by the donor has been investigated so far only by serologic studies. Thus, we addressed the issue of HHV-8 transmission in the transplantation setting by molecular methods. We exploited the high level variability of the orf-K1 gene and the polymorphism of theorf-73 gene of the HHV-8 genome to assess the genetic relatedness of the HHV-8 strains identified in the posttransplant KS lesions that developed, simultaneously, 20 months after transplantation, in 2 recipients of twin kidneys from the same cadaver donor. The 100% identity of nucleotide sequence of the most variable viral region and the presence of the same, singleorf-73 type in both patients provides strong molecular evidence of organ-related transmission of HHV-8 in the setting of transplantation.

Molecular evidence of organ-related transmission of Kaposi sarcoma–associated herpesvirus or human herpesvirus-8 in transplant patients

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3279-3281 ◽  
Author(s):  
Mario Luppi ◽  
Patrizia Barozzi ◽  
Gaia Santagostino ◽  
Raffaella Trovato ◽  
Thomas F. Schulz ◽  
...  
Keyword(s):  
Genetic Relatedness ◽  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Human Herpesvirus 8 ◽  
Molecular Evidence ◽  
Herpesvirus 8 ◽  
Transplant Patients ◽  
High Level

Abstract In transplant patients, Kaposi sarcoma (KS)-associated herpesvirus or human herpesvirus-8 (HHV-8) infection is associated with the development of KS, primary effusion lymphoma and Castleman disease. Whether HHV-8 is either reactivated in the recipient or transmitted by the donor has been investigated so far only by serologic studies. Thus, we addressed the issue of HHV-8 transmission in the transplantation setting by molecular methods. We exploited the high level variability of the orf-K1 gene and the polymorphism of theorf-73 gene of the HHV-8 genome to assess the genetic relatedness of the HHV-8 strains identified in the posttransplant KS lesions that developed, simultaneously, 20 months after transplantation, in 2 recipients of twin kidneys from the same cadaver donor. The 100% identity of nucleotide sequence of the most variable viral region and the presence of the same, singleorf-73 type in both patients provides strong molecular evidence of organ-related transmission of HHV-8 in the setting of transplantation.

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