Petros en kollega's hebben het
serum en de prostaatweefsel van mensen met prostaatkanker
onderzocht op antilichamen tegen resp. genetisch materiaal van XMRV
(m.b.v. PCR en FISH).
- De serologische test (test op antilichamen) en de testen waarbij genetisch materiaal opgespoord wordt,
geven vaak dezelfde uitslag (XMRV-positief of XMRV-negatief).
- in weerwil van studies die tot tegenovergestelde konklusies kwamen (klik hier)
lijkt er toch een direkte verband te zijn tussen genetische variaties van het
RNAse-L-gen (de zogenaamde R462Q variant) en de kans op een XMRV-infektie.
bij 40% van de mensen met de Q-variatie op beide chromosomen (de QQ-variant)
werd via antilichamen-test van het serum een XMRV-infektie vastgesteld.
New Investigation Supports Correlation Between XMRV and Prostate Cancer
Novel XMRV Retrovirus Diagnostic Test Developed
Philadelphia, PA, April 8, 2010
The recently discovered retrovirus, xenotropic murine leukemia virus-related virus (XMRV),
has been identified in some prostate cancer patients.
In light of conflicting data concerning XMRV,
standardized diagnostic testing is important to identify patients in which XMRV is present and
to determine whether it plays a role in the incidence of prostate cancer.
An article published in the April issue of Urology is a step in this direction
as researchers from Emory University report the successful development of an experimental clinical test for XMRV.
"We cannot as a scientific community begin to answer the basic questions of XMRV transmission,
frequency in the population, association with disease, etc. until we can effectively test for infection,"
according to lead investigator John A. Petros, MD, Associate Professor of Urology, Emory University School of Medicine and Veterans Administration Hospital.
Dr. Petros and co-investigators adapted technology developed in the HIV arena (neutralizing antibody assay)
and have developed a serum test that can identify patients who have previously been infected with the virus.
This assay has been rigorously confirmed by two independent labs and two independent technologies (PCR and FISH),
thus confidence in the accuracy of the test is high.
The mode of transmission of the virus is unknown.
No method is available to screen either blood or tissue donors for infection and no data are available regarding whether the virus can be transmitted by blood transfusion or tissue transplantation.
Dr. Petros comments, "
The public deserves to know if the next blood transfusion or organ donation will give them XMRV retrovirus,
an infection which lasts for life, and could possibly be related to prostate cancer.
The failure to develop accurate tests for this virus is
a serious public health oversight."
Although the assay used in the present report involved
the inhibition of infection of target cells by viral-like particles with the XMRV envelope protein expressed on their surface,
results also suggest that more standard serologic tests for antibodies against specific viral antigens can be developed in the future.
The authors conclude that
"our report adds to the growing body of evidence that
XMRV is indeed a novel gamma-retrovirus capable of infecting humans
and that at least some patients with prostate cancer have been infected with XMRV.
We have reported serologic evidence of infection and that the serology correlated with tissue-based assays.
The concordance of 3 independent methods of detecting infection
added confidence to the assertion that this recently discovered virus is real and possibly related to human disease.
Robust clinical assays are needed to detect XMRV infection, and much work remains to be done in determining whether XMRV is indeed an oncogenic virus or simply an associated epiphenomenon."
The article is
"XMRV Infection in Patients With Prostate Cancer: Novel Serologic Assay and Correlation With PCR and FISH"
by Rebecca S. Arnold, Natalia V. Makarova, Adeboye O. Osunkoya, Suganthi Suppiah, Takara A. Scott, Nicole A. Johnson, Sushma M. Bhosle,
Dennis Liotta, Eric Hunter, Fray F. Marshall, Hinh Ly, Ross J. Molinaro, Jerry L. Blackwell, and John A. Petros.
It appears in Urology, Volume 75, Issue 4 (April 2010) published by Elsevier.
XMRV infection in patients with prostate cancer: novel serologic assay and correlation with PCR and FISH.
Urology. 2010 Apr;75(4):755-61.
Arnold RS, Makarova NV, Osunkoya AO, Suppiah S, Scott TA, Johnson NA, Bhosle SM,
Liotta D, Hunter E, Marshall FF, Ly H, Molinaro RJ, Blackwell JL, Petros JA.
a serum-based assay
neutralizing antibodies to
the xenotropic murine leukemia virus-related virus (XMRV) retrovirus and
to use this assay
with polymerase chain reaction and
fluorescence in situ hybridization
patients with prostate cancer
previously exposed to XMRV infection and
those who carry
XMRV viral sequences in their prostate.
Patients who had undergone radical prostatectomy were enrolled,
and biologic specimens were obtained
The patients were genotyped for the R462Q RNASEL variant
using a TaqMan genotyping assay on DNA from the peripheral blood.
A serum assay that detects XMRV neutralizing antibodies
was developed and used to determine
which patients had serologic evidence of previous infection with XMRV virus.
Some of these patients were also tested for
the presence of XMRV nucleotide sequences
in their prostate
using polymerase chain reaction and
fluorescence in situ hybridization analysis.
At a serum dilution of 1:150,
our assay detected 11 (27.5%) of
40 patients with XMRV neutralizing antibodies, including
8 (40%) of 20 with the RNASEL genotype QQ and
3 (15%) of 20 with either the RQ or RR genotype.
These results were in complete concordance with 2 other assays
(polymerase chain reaction and fluorescence in situ hybridization),
which were designed to detect XMRV infection.
XMRV infects some patients with prostate cancer.
Neutralizing antibodies against XMRV correlated with
2 independent methods of detecting the virus in the prostate.
The antibody response suggests that
with clinical serologic assay development,
it might be possible to screen patients for XMRV infection.
The cases presented in the present report
provided biologic samples that can be used for
the development of a clinically relevant assay.
PMID: 20371060 [PubMed - in process]