Practical Management of Castleman's Disease

2016 ◽  
Vol 136 (1) ◽  
pp. 16-22
Author(s):  
Musa Fares Alzahrani ◽  
Mansoor Radwi ◽  
Heather A. Leitch
Keyword(s):  
Hiv Infection ◽  
Interleukin 6 ◽  
Lymphoproliferative Disorder ◽  
Treatment Options ◽  
Castleman’S Disease ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Castleman's Disease ◽  
Herpesvirus 8 ◽  
Hiv Negative

Castleman's disease (CD) is a rare lymphoproliferative disorder that is most commonly present in multicentric (MCD) form in association with HIV infection. Interleukin-6 (IL-6) and human herpesvirus-8 (HHV-8) play major roles in MCD pathogenesis. Important treatment options have recently become available, particularly with the introduction of IL-6 and IL-6 receptor inhibitors for the treatment of HIV-negative patients with MCD. Though advances in therapy may improve outcomes in some patients, the prognosis remains guarded, and a stratified approach to the management of MCD is needed.

scholarly journals Human Herpesvirus-8 Infection Associated with Kaposi Sarcoma, Multicentric Castleman's Disease, and Plasmablastic Microlymphoma in a Man with AIDS: A Case Report with Review of Pathophysiologic Processes

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Christian Eaton ◽  
Russell Dorer ◽  
David M. Aboulafia
Keyword(s):  
Lymph Node ◽  
Highly Active Antiretroviral Therapy ◽  
Castleman’S Disease ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Human Herpesvirus 8 ◽  
Castleman's Disease ◽  
Multicentric Castleman’S Disease ◽  
Herpesvirus 8 ◽  
Multicentric Castleman's Disease

Kaposi sarcoma (KS), multicentric Castleman's disease (MCD), and plasmablastic microlymphoma, are all linked to human herpesvirus-8 (HHV-8) infection and HIV-induced immunodeficiency. Herein, we describe the case of a Kenyan man diagnosed with HIV in 2000. He deferred highly active antiretroviral therapy (HAART) and remained in good health until his CD4+ count declined in 2006. He was hospitalized with bacterial pneumonia in 2008, after which he agreed to take HAART but did so sporadically. In 2010, he was hospitalized with fever, lymphadenopathy, pancytopenia, and an elevated HHV-8 viral load. A lymph node biopsy showed findings consistent with KS, MCD, and plasmablastic microlymphoma. Eight months after starting liposomal doxorubicin, Rituximab, and a new HAART regimen, he has improved clinically, and his HIV and HHV-8 viral loads are suppressed. These three conditions, found in the same lymph node, underscore the inflammatory and malignant potential of HHV-8, particularly in the milieu of HIV-induced immunodeficiency.

scholarly journals Genetic Analyses of Contributions of Viral Interleukin-6 Interactions and Signaling to Human Herpesvirus 8 Productive Replication

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Qian Li ◽  
Qiwang Xiang ◽  
Daming Chen ◽  
John Nicholas
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Interactions ◽  
Interleukin 6 ◽  
Kaposi's Sarcoma ◽  
Castleman’S Disease ◽  
Human Herpesvirus ◽  
Human Herpesvirus 8 ◽  
Signal Transducer ◽  
Herpesvirus 8 ◽  
Productive Replication

ABSTRACT Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) is a cytokine that is poorly secreted and localized largely to the endoplasmic reticulum (ER). It has been implicated, along with other HHV-8 proinflammatory and/or angiogenic viral proteins, in HHV-8-associated Kaposi’s sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD), in addition to an MCD-related disorder involving systemic elevation of proinflammatory cytokines, including vIL-6 and human IL-6 (hIL-6). In these diseases, lytic (productive) replication, in addition to viral latency, is believed to play a critical role. Proreplication activity of vIL-6 has been identified experimentally in PEL and endothelial cells, but the relative contributions of different vIL-6 interactions have not been established. Productive interactions of vIL-6 with the IL-6 signal transducer, gp130, can occur within the ER, but vIL-6 also interacts in the ER with a nonsignaling receptor called vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2), calnexin, and VKORC1v2- and calnexin-associated proteins UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) and glucosidase II (GlucII). Here, we report the systematic characterization of interaction-altered vIL-6 variants and the lytic phenotypes of recombinant viruses expressing selected variants. Our data identify the critical importance of vIL-6 and its ER-localized activity via gp130 to productive replication in inducible SLK (epithelial) cells, absence of detectable involvement of vIL-6 interactions with VKORC1v2, GlucII, or UGGT1, and the insufficiency and lack of direct contributory effects of extracellular signaling by vIL-6 or hIL-6. These findings, obtained through genetics-based approaches, complement and extend previous analyses of vIL-6 activity. IMPORTANCE Human herpesvirus 8 (HHV-8)-encoded viral interleukin-6 (vIL-6) was the first viral IL-6 homologue to be identified. Experimental and clinical evidence suggests that vIL-6 is important for the onset and/or progression of HHV-8-associated endothelial-cell and B-cell pathologies, including AIDS-associated Kaposi’s sarcoma and multicentric Castleman’s disease. The protein is unusual in its poor secretion from cells and its intracellular activity; it interacts, directly or indirectly, with a number of proteins beyond the IL-6 signal transducer, gp130, and can mediate activities through these interactions in the endoplasmic reticulum. Here, we report the characterization with respect to protein interactions and signal-transducing activity of a panel of vIL-6 variants and utilization of HHV-8 mutant viruses expressing selected variants in phenotypic analyses. Our findings establish the importance of vIL-6 in HHV-8 productive replication and the contributions of individual vIL-6-protein interactions to HHV-8 lytic biology. This work furthers understanding of the biological significance of vIL-6 and its unique intracellular interactions.

High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric Castleman disease in HIV-infected patients

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2069-2073 ◽  
Author(s):  
Eric Oksenhendler ◽  
Guislaine Carcelain ◽  
Yoshiyasu Aoki ◽  
Emmanuelle Boulanger ◽  
Anne Maillard ◽  
...  
Keyword(s):  
Viral Load ◽  
Interleukin 6 ◽  
Lymphoproliferative Disorder ◽  
Human Herpesvirus ◽  
Castleman Disease ◽  
Human Herpesvirus 8 ◽  
C Reactive Protein ◽  
Herpesvirus 8 ◽  
Multicentric Castleman Disease ◽  
Reactive Protein

Abstract 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 human herpesvirus 8 (HHV8) infection. In a prospective study of 23 HIV-infected patients with MCD, clinical symptoms of MCD were present at 45 visits, whereas patients were in chemotherapy-induced clinical remission at 50 visits. Symptoms were associated with a high level of serum C reactive protein, high HHV8 viral load in peripheral blood mononuclear cells, and high plasma human IL-6 and IL-10 levels. Strong correlations between plasma IL-6 and plasma IL-10 with the HHV8 viral load suggest that both cytokines may be involved in the pathogenesis of this virus-associated lymphoproliferative disorder.

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