Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3474-3475
CORRESPONDENCE
Absence of a Correlation Between Kaposi's Sarcoma-Associated
Herpesvirus (KSHV/HHV-8) and Multiple Myeloma
 |
LETTER |
To the Editor:
Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) has been found
within tumor tissue in Kaposi's sarcoma, Castleman's disease, and
primary effusion lymphoma (PEL). KSHV has been shown to bear several
genes with functional homology to cellular genes, including interleukin-6 (IL-6).1 Human IL-6 may stimulate myeloma
cell growth, and reports by Rettig et al2,3 and Said et
al4 have recently shown that KSHV could be isolated from
cultured bone dendritic marrow cells from patients with multiple
myeloma (MM), Waldenstrom's macroglobulinemia, or primary amyloidosis, but not from normal individuals or patients with other hematological diseases. To investigate this association we looked for antibodies to
KSHV in sera, and for KSHV genome in bone marrow samples from patients
with MM and other diseases.
One hundred eighty individuals were enrolled (Table
1): 99 patients with advanced-stage MM, 2 patients with monoclonal gammopathy of undetermined significance
(MGUS), 14 patients with non-Hodgkin's lymphoma, 19 patients with
breast cancer, 34 normal individuals, 6 Epstein-Barr virus (EBV)
IgG/IgM seropositive individuals, 2 human immunodeficiency virus
(HIV)-positive patients with Kaposi's sarcoma, and 4 HIV-positive
patients without Kaposi's sarcoma. Patient groups (>10 points) were
matched for age. Serum probes of myeloma, lymphoma, and breast cancer
patients were taken between 1 and 3 weeks before peripheral blood stem
cell transplantation and frozen. Serum was used in an immunofluorescent
assay to detect antibodies to lytic-phase proteins expressed in KS-1
cells, a PEL-derived EBV
cell line that supports KSHV
replication after stimulation. Sera from patients with Kaposi's
sarcoma taken as a positive control stained positive for KSHV. To
exclude false-positive results due to the known homology between KSHV
and EBV antigens, we tested sera from 6 patients with EBV reactivation.
These sera showed no KSHV seropositivity. Sera from HIV patients
without Kaposi's sarcoma also showed negative results. Finally,
polyvalent IgG (Endobulin; Baxter-Immuno, Heidelberg, Germany),
administered to 72 of 99 patients with MM, was tested to exclude
false-positive staining. We found no difference in seroprevalence of
KSHV between MM, NHL, breast cancer patients, or normal individuals
(Table 1).
In view of the low HHV-8 seroprevalence in MM we looked at the
remission status at the time of sampling. Complete remission was found
in 20% of cases, arguing against an inhibitory effect of paraprotein.
In addition, concurrent tests for EBV and CMV IgG antibodies showed no
significant difference between control and MM patients (90%/91% EBV
IgG+, 67%/75% CMV IgG+).
From 43 patients with advanced-stage MM we tested fresh bone marrow
aspirate samples for KSHV genome. The probes were analyzed for the
presence of the virus genome by a nested polymerase chain reaction
(PCR) that amplifies the KS330 233 sequence of KSHV. In only one
patient could this sequence be detected, and this patient was also
seropositive for KSHV. Dendritic cells cultivated from bone marrow from
25 of these patients were also negative for KSHV genome (manuscript
submitted).
Our results confirm the French and United Kingdom5,6
results that report no increased seroprevalence for KSHV in MM compared with healthy controls or other disease groups, and contradict that of
Alsina et al.7 In addition we failed to find evidence by
nested PCR of the presence of KSHV genome in the majority of MM
patients or controls, either in bone marrow aspirates or dendritic cells cultured from those aspirates. It is difficult to reconcile our
results with the PCR findings reported by Rettig et al, unless one
assumes that exceedingly low levels of infected dendritic cells are
capable of inducing antigen-specific B-cell tolerance within the bone
marrow. It has been shown in studies with transgenic mice that antigen
located in the bone marrow leads to clonal deletion or anergy of
antigen-specific B cells8; however, such a mechanism has
not yet been described for KSHV. To investigate this possibility we are
currently following the KSHV antibody status of seropositive MM
patients and controls in longitudinal studies.
G. Schönrich
M. Raftery
P. Schnitzler
Hygiene-Institut
der Universität Heidelberg
Abteilung für Medizinische
Virologie
Heidelberg, Germany
U. Rohr
H. Goldschmidt
Poliklinik der Universität
Heidelberg
Heidelberg, Germany
| |
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