HHV‐8 infection status of AIDS‐unrelated and AIDS‐associated multicentric Castleman's disease

Multicentric Castleman's disease (MCD) is a clinicopathologically defined entity characterized by systemic lymphadenopathy with unique pathomorphology such as angiosclerosis, blood vessel proliferation in and around follicles, and plasmacytosis. While its pathogenesis has remained unclarified for many years, identification of the human herpesvirus 8 (HHV‐8) in at least some MCD cases has opened new perspectives in this field. Because previous reports have described many inconsistencies regarding HHV‐8 positivity in MCD, we intended to clarify this issue by the introduction of more convincing methodologies. For this investigation, we introduced two antibodies produced in our laboratories that recognize a latent gene product ORF73 and a lytic gene product ORF59, together with two well‐recognized methods, in situ hybridization for the detection of lytic phase transcript T1.1/nut‐1, and genomic polymerase chain reaction (PCR). Eighty‐two cases of MCD were collected from Japan (n= 75) and France (n= 7). In three cases, the patients were suffering from acquired immunodeficiency syndrome (AIDS). Immunohistochemistry and in situ hybridization showed identical results: only three out of 82 cases were positively stained, and all the positive cases were found to be the patients with AIDS. Genomic PCR was done in 43 cases, and only one case produced positive results: the only AIDS case among the 43 cases studied by genomic PCR. Histopathologically, the HHV‐8‐positive cases showed the highest intensity of angiosclerosis and germinal center / perifollicular vascular proliferation, while plasmacytosis was not severe in the HHV‐8‐positive cases. Some of the HHV‐8‐negative MCD cases displayed similar histopathology, but at a far less intense level, except for the plasmacytosis. These results suggest that: (i) all three of the HHV‐8‐positive MCD patients in the present group are the patients with AIDS; and (ii) HHV‐8‐positive MCD patients develop typical but marked angiosclerosis and vascular proliferation that might be differentiated from HHV‐8‐negative MCD patients, who showed far less intense changes.

[1]  S. Mori,et al.  Identification of Antigenic Proteins Encoded by Human Herpesvirus 8 and Seroprevalence in the General Population and among Patients with and without Kaposi's Sarcoma , 2000, Journal of Virology.

[2]  S. Mori,et al.  Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi's sarcoma, and multicentric Castleman's disease. , 2000, Virology.

[3]  M. Corbellino,et al.  Differential viral protein expression in Kaposi's sarcoma-associated herpesvirus-infected diseases: Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. , 2000, The American journal of pathology.

[4]  C. Boshoff,et al.  HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma. , 2000, Blood.

[5]  Koichiro Nakamura,et al.  Human Herpesvirus 8–Associated Solid Lymphomas that Occur in AIDS Patients Take Anaplastic Large Cell Morphology , 2000, Modern Pathology.

[6]  S. Sakurada,et al.  Expression and antigenicity of human herpesvirus 8 encoded ORF59 protein in AIDS‐associated Kaposi's sarcoma , 1999, Journal of medical virology.

[7]  C. Boshoff,et al.  Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa , 1999, British Journal of Cancer.

[8]  H. Satoh,et al.  Establishing and characterizing a CD30‐positive cell line harboring HHV‐8 from a primary effusion lymphoma , 1999, Journal of medical virology.

[9]  S. Mori,et al.  High expression of HHV-8-encoded ORF73 protein in spindle-shaped cells of Kaposi's sarcoma. , 1999, The American journal of pathology.

[10]  E. Jaffe,et al.  Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6. , 1999, Blood.

[11]  C. Boshoff,et al.  Characterization of Monoclonal Antibodies Raised against the Latent Nuclear Antigen of Human Herpesvirus 8 , 1999, Journal of Virology.

[12]  E. van Marck,et al.  Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  A. Utsunomiya,et al.  Expression of vascular endothelial growth factor in sera and lymph nodes of the plasma cell type of Castleman's disease , 1999, British journal of haematology.

[14]  E. Jaffe,et al.  Expression of human herpesvirus-8 oncogene and cytokine homologues in an HIV-seronegative patient with multicentric Castleman's disease and primary effusion lymphoma. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[15]  R. Ricciardi,et al.  Cloning and Functional Analysis of Kaposi’s Sarcoma-Associated Herpesvirus DNA Polymerase and Its Processivity Factor , 1998, Journal of Virology.

[16]  B. Chandran,et al.  Reactivities of human sera with human herpesvirus-8-infected BCBL-1 cells and identification of HHV-8-specific proteins and glycoproteins and the encoding cDNAs. , 1998, Virology.

[17]  B. Chandran,et al.  Identification and characterization of human herpesvirus-8 lytic cycle-associated ORF 59 protein and the encoding cDNA by monoclonal antibody. , 1998, Virology.

[18]  M. Corbellino,et al.  Expression of a virus-derived cytokine, KSHV vIL-6, in HIV-seronegative Castleman's disease. , 1997, The American journal of pathology.

[19]  H. Stein,et al.  Expression of vascular endothelial growth factor in lymphomas and castleman's disease , 1997, The Journal of pathology.

[20]  Yi Fang Liu,et al.  Kaposi's sarcoma‐associated herpesvirus sequences in benign lymphoid proliferations not associated with human immunodeficiency virus , 1997, Cancer.

[21]  L. Rainbow,et al.  The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen , 1997, Journal of virology.

[22]  M. Kawashima,et al.  Human herpesvirus 8 DNA is rarely found in Bowen's disease of non‐immunosuppressed patients , 1997, The British journal of dermatology.

[23]  Y. Kwong,et al.  Absence of Kaposi's sarcoma associated herpesvirus-like DNA sequences (KSHV) in HIV-negative multicentric Castleman's disease complicated by KSHV-positive Kaposi's sarcoma. , 1997, British journal of haematology.

[24]  W. Zhong,et al.  Characterization of ribonucleoprotein complexes containing an abundant polyadenylated nuclear RNA encoded by Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) , 1997, Journal of virology.

[25]  A. Haase,et al.  Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells , 1997, Journal of virology.

[26]  F. Neipel,et al.  Human herpesvirus 8 encodes a homolog of interleukin-6 , 1997, Journal of virology.

[27]  G. Gaidano,et al.  Human herpesvirus type-8 (HHV-8) in haematopoietic neoplasia. , 1997, Leukemia & lymphoma.

[28]  E. Cesarman,et al.  Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. , 1996, Blood.

[29]  C. Cockerell,et al.  Localization of human herpes-like virus type 8 in vascular endothelial cells and perivascular spindle-shaped cells of Kaposi's sarcoma lesions by in situ hybridization. , 1996, The American journal of pathology.

[30]  M. McGrath,et al.  Lytic growth of Kaposi's sarcoma–associated herpesvirus (human herpesvirus 8) in culture , 1996, Nature Medicine.

[31]  J. Diebold,et al.  Kaposi sarcoma-associated herpes-like virus (human herpesvirus type 8) DNA sequences in multicentric Castleman's disease: is there any relevant association in non-human immunodeficiency virus-infected patients? [letter; comment] , 1996 .

[32]  C. Boshoff,et al.  Kaposi's sarcoma-associated herpesvirus infects endothelial and spindle cells , 1995, Nature Medicine.

[33]  F. Sigaux,et al.  Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. , 1995, Blood.

[34]  E. Cesarman,et al.  Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. , 1995, The New England journal of medicine.

[35]  P. Moore,et al.  Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and those without HIV infection. , 1995, The New England journal of medicine.

[36]  E. Cesarman,et al.  Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. , 1994, Science.

[37]  S. Hsu,et al.  Interleukin-6, but not interleukin-4, is expressed by Reed-Sternberg cells in Hodgkin's disease with or without histologic features of Castleman's disease. , 1992, The American journal of pathology.

[38]  J. Diebold,et al.  Interleukin-6 gene expression in Castleman's disease. , 1991, Blood.

[39]  P. Isaacson,et al.  Multicentric Castleman's disease in association with a solitary plasmacytoma: a case report , 1990, Histopathology.

[40]  T. Komori,et al.  Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman's disease. , 1989, Blood.

[41]  K. Mullis,et al.  Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. , 1988, Science.

[42]  P. Banks,et al.  A systemic lymphoproliferative disorder with morphologic features of Castleman's disease: Pathological findings in 15 patients , 1983, The American journal of surgical pathology.