Analysis of the Human Herpesvirus 8 (HHV-8) Genome and HHV-8 vIL-6 Expression in Archival Cases of Castleman Disease at Low Risk for HIV Infection

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.

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Immune reconstitution inflammatory syndrome, human herpesvirus 8 viremia, and HIV-associated multicentric Castleman disease

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2016.05.005 ◽

2016 ◽

Vol 48 ◽

pp. 49-51 ◽

Cited By ~ 5

Author(s):

Marc O. Siegel ◽

Sanaz Ghafouri ◽

Ravi Ajmera ◽

Gary L. Simon

Keyword(s):

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

Human Herpesvirus ◽

Castleman Disease ◽

Human Herpesvirus 8 ◽

Herpesvirus 8 ◽

Multicentric Castleman Disease ◽

Inflammatory Syndrome

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Human Herpesvirus-8 Negative Multicentric Castleman Disease in a Patient with Human Immunodeficiency Virus Treated with Highly Active Antiretroviral Therapy and Chemotherapy

Cureus ◽

10.7759/cureus.5530 ◽

2019 ◽

Author(s):

S. Caleb Freeman ◽

Janani Baskaran ◽

Maryam Gbadamosi-Akindele

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Human Herpesvirus ◽

Castleman Disease ◽

Human Herpesvirus 8 ◽

Herpesvirus 8 ◽

Multicentric Castleman Disease ◽

Highly Active ◽

Immunodeficiency Virus

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

Blood ◽

10.1182/blood-2018-11-852442 ◽

2019 ◽

Vol 133 (11) ◽

pp. 1186-1190 ◽

Cited By ~ 9

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.

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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 ◽

10.1182/blood.v96.6.2069 ◽

2000 ◽

Vol 96 (6) ◽

pp. 2069-2073 ◽

Cited By ~ 239

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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Human Herpesvirus-8–Positive Microvenular Hemangioma in POEMS Syndrome

Archives of Pathology & Laboratory Medicine ◽

10.5858/2003-127-1034-hhmhip ◽

2003 ◽

Vol 127 (8) ◽

pp. 1034-1036 ◽

Cited By ~ 2

Author(s):

S. David Hudnall ◽

Tiansheng Chen ◽

Kelty Brown ◽

Tiffany Angel ◽

Mary R. Schwartz ◽

...

Keyword(s):

Endothelial Cells ◽

African American Woman ◽

American Woman ◽

Human Herpesvirus ◽

Castleman Disease ◽

Human Herpesvirus 8 ◽

Herpesvirus 8 ◽

First Case ◽

Initial Symptoms ◽

Night Sweats

Abstract We report a case of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome in a 55-year-old African American woman in which human herpesvirus-8 (HHV-8) was demonstrated within rare lymphocytes in a Castleman disease lymph node biopsy and numerous endothelial cells and lymphocytes in a microvenular hemangioma skin biopsy. Initial symptoms and findings of night sweats, weight loss, anorexia, generalized lymphadenopathy, and hemangiomas improved after chemotherapy with cyclophosphamide and prednisone. However, in the year following the initial diagnosis, the patient suffered from recurrent bouts of night sweats, gastroparesis, and lymphadenopathy, which required further treatment with plasmapheresis, cyclophosphamide, prednisone, and rituximab. One year later, the patient is asymptomatic but has persistent gammopathy. Although HHV-8 has previously been detected in POEMS-associated Castleman disease tissue, to our knowledge, this is the first case report in which HHV-8 has been directly demonstrated within the endothelial cells of a POEMS-associated hemangioma.

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

Blood ◽

10.1182/blood.v96.9.3279.h8003279_3279_3281 ◽

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.

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