scholarly journals An Interleukin‐6–Related Systemic Inflammatory Syndrome in Patients Co‐Infected with Kaposi Sarcoma–Associated Herpesvirus and HIV but without Multicentric Castleman Disease

2010 ◽  
Vol 51 (3) ◽  
pp. 350-358 ◽  
Author(s):  
Thomas S. Uldrick ◽  
Victoria Wang ◽  
Deirdre O’Mahony ◽  
Karen Aleman ◽  
Kathleen M. Wyvill ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Multicentric Castleman Disease ◽  
Inflammatory Syndrome

scholarly journals Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease

Blood ◽  
2013 ◽  
Vol 122 (26) ◽  
pp. 4189-4198 ◽  
Author(s):  
Mark N. Polizzotto ◽  
Thomas S. Uldrick ◽  
Victoria Wang ◽  
Karen Aleman ◽  
Kathleen M. Wyvill ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Multicentric Castleman Disease ◽  
Key Points

Key PointsHuman IL-6 and a viral IL-6 homolog encoded by KSHV/HHV8 can independently or together lead to flares of KSHV-associated MCD. KSHV-MCD disease flares were more severe where both human and viral IL-6 were elevated, suggesting they jointly contribute to severity.

Detection of viral interleukin-6 in Kaposi sarcoma–associated herpesvirus–linked disorders

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 2173-2176 ◽  
Author(s):  
Yoshiyasu Aoki ◽  
Robert Yarchoan ◽  
Kathleen Wyvill ◽  
Shin-ichiro Okamoto ◽  
Richard F. Little ◽  
...  
Keyword(s):  
United States ◽  
Interleukin 6 ◽  
Blood Donors ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
The United States ◽  
Castleman Disease ◽  
Hiv Status ◽  
Hiv Patients ◽  
Multicentric Castleman Disease

Abstract Expression of a viral interleukin-6 (vIL-6) has been detected in certain Kaposi sarcoma (KS)–associated herpesvirus positive (KSHV+) lesions. The release of vIL-6 systemically and its contribution to the pathogenesis of HIV-related malignancies was studied. Serum vIL-6 was detected in 13 (38.2%) of 34 HIV+ patients with KS, in 6 (85.7%) of 7 HIV+patients with primary effusion lymphoma (PEL) and/or multicentric Castleman disease (MCD), and in 18 (60.0%) of 30 HIV+, mostly homosexual, individuals without KS, MCD, or PEL. By contrast, serum vIL-6 was detected in only 3 (23.1%) of 13 patients with classic KS, 1 (2.5%) of 40 blood donors from the United States, and 4 (19.0%) of 21 blood donors from Italy. Circulating vIL-6 levels were associated with HIV+ status (P < .0001). However, within the HIV+ cohort, serum vIL-6 levels were not associated with the occurrence of KSHV-associated malignancies (P = .43).

The Kaposi sarcoma–associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 649-654 ◽  
Author(s):  
Jiabin An ◽  
Alan K. Lichtenstein ◽  
Gregory Brent ◽  
Matthew B. Rettig
Keyword(s):  
Interleukin 6 ◽  
Primary Effusion Lymphoma ◽  
Acute Infection ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Nuclear Antigen ◽  
Response Element ◽  
Multicentric Castleman Disease ◽  
Stromal Cell Line ◽  
Infected Cells

Abstract Cellular interleukin 6 (IL-6) is an important growth factor for Kaposi sarcoma– associated herpesvirus (KSHV)–associated neoplasms, which include human immunodeficiency virus (HIV)–related and -unrelated cases of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Increased IL-6 levels are found in tissues affected with these diseases, and KSHV exists in a latent state in the majority of virally infected cells. In addition, acute infection with KSHV up-regulates IL-6 expression in endothelial cells. Thus, the hypothesis was considered that a latent KSHV gene product up-regulates IL-6 expression. To evaluate this hypothesis, the KSHV latency-associated nuclear antigen (LANA) was expressed in human embryonal kidney 293 cells and a bone marrow stromal cell line. LANA up-regulates IL-6 expression by inducing transcription from the IL-6 promoter, and the AP1 response element within the IL-6 promoter is necessary for and mediates IL-6 up-regulation by LANA. Thus, LANA may play a key pathophysiologic role in KSHV-associated neoplasms by functioning to up-regulate expression of IL-6.

scholarly journals Induction of Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral Interleukin-6 by X-Box Binding Protein 1

2015 ◽  
Vol 90 (1) ◽  
pp. 368-378 ◽  
Author(s):  
Duosha Hu ◽  
Victoria Wang ◽  
Min Yang ◽  
Shahed Abdullah ◽  
David A. Davis ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Interleukin 6 ◽  
Promoter Region ◽  
Binding Protein ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Lytic Gene ◽  
Response Elements ◽  
Multicentric Castleman Disease

ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentric Castleman disease (MCD). The KSHV life cycle has two principal gene repertoires, latent and lytic. KSHV viral interleukin-6 (vIL-6), an analog of human IL-6, is usually lytic; production of vIL-6 by involved plasmablasts is a central feature of KSHV-MCD. vIL-6 also plays a role in PEL and KS. We show that a number of plasmablasts from lymph nodes of patients with KSHV-MCD express vIL-6 but not ORF45, a KSHV lytic gene. We further show that vIL-6 is directly induced by the spliced (active) X-box binding protein-1 (XBP-1s), a transcription factor activated by endoplasmic reticulum (ER) stress and differentiation of B cells in lymph nodes. The promoter region of vIL-6 contains several potential XBP-response elements (XREs), and two of these elements in particular mediate the effect of XBP-1s. Mutation of these elements abrogates the response to XBP-1s but not to the KSHV replication and transcription activator (RTA). Also, XBP-1s binds to the vIL-6 promoter in the region of these XREs. Exposure of PEL cells to a chemical inducer of XBP-1s can induce vIL-6. Patient-derived PEL tumor cells that produce vIL-6 frequently coexpress XBP-1, and immunofluorescence staining of involved KSHV-MCD lymph nodes reveals that most plasmablasts expressing vIL-6 also coexpress XBP-1. These results provide evidence that XBP-1s is a direct activator of KSHV vIL-6 and that this is an important step in the pathogenesis of KSHV-MCD and PEL.IMPORTANCEKaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (KSHV-MCD) is characterized by severe inflammatory symptoms caused by an excess of cytokines, particularly KSHV-encoded viral interleukin-6 (vIL-6) produced by lymph node plasmablasts. vIL-6 is usually a lytic gene. We show that a number of KSHV-MCD lymph node plasmablasts express vIL-6 but do not have full lytic KSHV replication. Differentiating lymph node B cells express spliced (active) X-box binding protein-1 (XBP-1s). We show that XBP-1s binds to the promoter of vIL-6 and can directly induce production of vIL-6 through X-box protein response elements on the vIL-6 promoter region. We further show that chemical inducers of XBP-1s can upregulate production of vIL-6. Finally, we show that most vIL-6-producing plasmablasts from lymph nodes of KSHV-MCD patients coexpress XBP-1s. These results demonstrate that XBP-1s can directly induce vIL-6 and provide evidence that this is a key step in the pathogenesis of KSHV-MCD and other KSHV-induced diseases.

scholarly journals “Chronic Disseminated Aspergillosis,” a Novel Fungal Immune Reconstitution Inflammatory Syndrome

2020 ◽  
Vol 7 (11) ◽  
Author(s):  
Annabelle Pourbaix ◽  
Romain Guery ◽  
Julie Bruneau ◽  
Estelle Blanc ◽  
Gregory Jouvion ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Clinical Presentation ◽  
Castleman Disease ◽  
Disease Symptoms ◽  
Disseminated Candidiasis ◽  
Multicentric Castleman Disease ◽  
Chronic Disseminated Candidiasis ◽  
Disseminated Aspergillosis ◽  
Inflammatory Syndrome

Abstract We report a case of chronic hepatosplenic aspergillosis following immune reconstitution complicating colic aspergillosis in an AIDS patient with multicentric Castleman disease. Symptoms mimicked the clinical presentation of chronic disseminated candidiasis and responded to corticosteroid. This emerging entity enlarges the spectrum of fungal immune reconstitution inflammatory syndrome in the HIV setting.

Coexistence of disseminated Kaposi sarcoma and multicentric Castleman disease in an HIV-infected patient under viral suppression

2021 ◽  
Vol 32 (3) ◽  
pp. 286-289
Author(s):  
I-Fan Lin ◽  
Jiun-Nong Lin ◽  
Tsung-Heng Tsai ◽  
Chao-Tien Hsu ◽  
Yu-Ying Wu ◽  
...  
Keyword(s):  
Viral Load ◽  
Viral Suppression ◽  
Liposomal Doxorubicin ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Severe Thrombocytopenia ◽  
Multicentric Castleman Disease ◽  
Progressive Pancytopenia ◽  
One Year ◽  
Cd4 T Cell Count

Coexistence of multicentric Castleman disease and Kaposi sarcoma is rare and might be missed without an experienced pathologists’ interpretation. A 46-year-old man had been diagnosed with HIV infection and treated with combination antiretroviral therapy of dolutegravir/abacavir/lamivudine (Triumeq) for one year. The latest viral load was 49 copies/mL and CD4 T-cell count was 192 cells/uL. He was admitted due to fever off and on, splenomegaly, general lymphadenopathy, and severe thrombocytopenia for two months. Biopsy of a purplish skin lesion and gastric tissue showed Kaposi sarcoma. The pathology of inguinal lymph nodes revealed coexistence of Kaposi sarcoma and multicentric Castleman disease. The plasma Kaposi sarcoma herpesvirus viral load was 365,000 copies/mL. During hospitalization, progressive pancytopenia and spiking fever persisted, and he died of multi-organ failure before completion of chemotherapeutic treatments with rituximab plus liposomal doxorubicin.

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.

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