Evidence against KSHV infection in the pathogenesis of multiple myeloma

Kaposi's sarcoma-associated herpesvirus (KSHV) is likely to play a pathogenic role in Kaposi's sarcoma, body cavity-based primary effusion lymphoma and a subset of Castleman's disease. A recent polymerase chain reaction (PCR)-based study reported an association between KSHV and multiple myeloma (MM). We searched for KSHV infection in MM patients by serology, PCR and immunohistochemistry. In addition, we cultured dendritic and stromal cells from MM patients. KSHV antibodies were universally absent from MM patients (0/25) whereas EBV antibodies were nearly ubiquitous (24/25). All of the bone marrow biopsies (0/16) and negative controls (0/4) were vIL-6 negative. None of the bone marrow aspirates (0/6) or biopsies (0/3), peripheral blood mononuclear cells (0/8), mononuclear apheresis cells (0/5) or dendritic cell cultures (0/5) were positive by PCR. One of the MM stromal cell cultures (1/7) was positive for KSHV DNA by PCR and weakly positive on direct southern hybridization using a probe to the terminal repeat region. However, this same patient was PCR negative using another primer set, KSHV seronegative, and negative for vIL-6 immunostaining. Our results suggest that the KSHV DNA positivity rate among MM patients is much lower than previously reported.