Exacerbations of Clinical Symptoms in Human Immunodeficiency Virus Typ 1-Infected Patients with Multicentric Castleman's Disease Are Associated with a High Increase in Kaposi's Sarcoma Herpesvirus DNA Load in Peripheral Blood Mononuclear Cells

Abstract

The epidemiologic link between multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) and the high frequency of KS herpesvirus (KSHV) detection in both diseases raise the question of a role of this new virus in the pathogenesis of MCD. To explore this hypothesis, the KSHV DNA load was investigated in peripheral blood mononuclear cells of 3 human immunodeficiency virus (HIV)-infected patients with MCD at different points during the clinical course. Clinical parameters, such as fever and the presence of lymphadenopathy, were systematically assessed. Hemogram and C-reactive protein level determinations were performed as standard procedures. KSHV DNA load was investigated by means of semiquantitative polymerase chain reaction assay using peripheral blood mononuclear cells of the patients. A correlation between the variation in clinical and biologic parameters related to MCD and KSHV DNA load was found, suggesting a close relationship between KSHV and MCD in HIV-1-infected patients.

Long-term remission of Kaposi sarcoma–associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy

“…Detection of the virus in secondary lymphoid organs is essential for diagnosis because histologic findings do not allow distinction between KSHV-negative and KSHV-positive MCD. 2,5,6,13,14 Elevated viral burden in PBMC may be a characteristic feature of this disorder, 15 and blood viral monitoring may be the most accurate marker of disease activity and response to therapy 15,16 -similar to circulating EBV DNA levels in lymphoproliferative disorders after transplantation. 17 Antiherpesvirus therapy has been advocated in KSHV-related MCD.…”

The pleiotropic effects of Kaposi's sarcoma herpesvirus

“…This interpretation is supported by reports that the intensity of clinical symptoms in MCD patients, such as fever, or laboratory parameters reflecting disease activity, such as C-reactive protein, correlate with the KSHV viral load in peripheral blood [131,132]. Fluctuations of KSHV viral load in HIV-infected patients with MCD also mirror fluctuations in the plasma levels of human IL-6 and IL-10, and plasma HIV RNA copy numbers, indicating that active HIV infection can increase the severity of MCD by increasing KSHV viral load [131,132].…”

“…Fluctuations of KSHV viral load in HIV-infected patients with MCD also mirror fluctuations in the plasma levels of human IL-6 and IL-10, and plasma HIV RNA copy numbers, indicating that active HIV infection can increase the severity of MCD by increasing KSHV viral load [131,132].…”

“…The parallel fluctuations of KSHV viral load and cytokines such as IL-6 and IL-10 in active MCD [131] point to a role for paracrine effects induced by active viral replication. In addition to cellular cytokines induced by latent or lytic viral proteins such [134][135][136], as well as the human myeloma cell line INA-6 [137] in vitro and to promote colony formation of human CD34-positive bone marrow progenitor cells [138].…”

Kaposi’s Sarcoma-Associated Virus Governs Gene Expression Profiles Toward B Cell Transformation

“…MCD is a B cell lymphoma morphologically resembling plasmablasts without undergoing a germinal center reaction (Parravicini et al, 2000). It is unclear how this disease is established but a KSHV viral load is a decisive factor for exacerbation of MCD (Grandadam et al, 1997) and thus KSHV should have a role in MCD pathogenesis. High level interleukin 6 (IL-6) is a well-known fact in MCD and should do something in MCD pathogenesis (Oksenhendler et al, 1996).…”