| Abstract |
The Kaposis sarcoma-associated herpesvirus (KSIIV), or human herpesvirus 8
(HHV-8) is consistently present in primary effusion lymphomas (PEL), a
rare distinctive type of B cell non-Hodgkin's lymphoma usually originating
in the body cavities as an effusion. Involvement of an effusion by
malignant myeloma plasma cells is also distinctly rare, occurring in less
than 1% of cases of multiple myeloma (MM). We have identified two HIV-
negative patients with MM who in addition had a myelomatous effusion. Both
myelomatous effusions contained KSHV genome, as evaluated by Southern and
Northern blot analyses. KSHV was visualized within all the malignant
plasma cells by indirect immunofluorescence assays (IFA). A tumor sample
from one of these patients, obtained 4 months before the development of
the pleural effusion, had no detectable KSHV by Southern blot analysis,
suggesting that KSHV infection of the myeloma cells in the pleural fluid
was a secondary event related to tumor progression. EBV was not detected
in either case. We have established a cell line from one of these cases.
called ME-1. We also screened 21 existing MM cell lines for the presence of
KSHV, and failed to identify any other KSHV-positive line. ME-1 cells
retain a high episomal copy number of KSHV, and preserve all
characteristics of malignant plasma cells, including morphology,
cytoplasmic immunoglobulin and expression of plasma cell-associated
antigens. KSHV can be induced to replicate in ME-1 cells by treatment with
TPA, and infectious particles can be purified. KSHV has been previously
reported to be present in bone marrow stromal cells of patients with MM.
However, patients with MM do not have serologic reactivity to this virus
as determined employing immunofluorescence assays (IFA) using PEL cell lines
as substrates, or ELISA using virus purified from such cell lines. We
hypothesized that this lack of recognition could be due to the presence
of a different viral strain of KSHV in MM patients, that does not cross-
react serologically with that of PEL. We tested whether ME-1 contained
this putative "MM virus", and therefore contained viral antigens
recognized by sera from other patients with MM. We examined serum obtained
from 59 patients with MM or MGUS for the presence of antibodies to KSHV.
IFA using ME-1 cells showed positivity in only two samples from the same
patient, who had homosexuality as a risk factor for KSHV infection. Sera
from five patients with KS and one patient with PEL recognized both
latent and lytic antigens in ME-1 cells. Therefore, we could not
demonstrate the presence of a different, MM-associated virus in this cell
line. These results represent the first demonstration of KSHV within
malignant myeloma plasma cells, and the development of the first KSHV-
positive myeloma cell line. The presence of KSHV in myclomatous effusions
but not in plasma cells in other forms of multiple myeloma is highly
reminiscent of the presence of KSHV in PEL but not in other types of non-
Hodgkin's lymphoma, and further suggests an association behmen KSHV and
the effusion phenotype.
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