XMRV Infection in Patients With Prostate Cancer: Petrosa et al Apr 5 '10

[leelaplay]

Urology Volume 75, Issue 4, April 2010, Pages 755-761
doi:10.1016/j.urology.2010.01.038 | How to Cite or Link Using DOI
Copyright 2010 Published by Elsevier Inc.
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Cancer

XMRV Infection in Patients With Prostate Cancer: Novel Serologic Assay and Correlation With PCR and FISH

Rebecca S. Arnolda, b, Natalia V. Makarovac, Adeboye O. Osunkoyaa, b, d, Suganthi Suppiahd, Takara A. Scotta, Nicole A. Johnsona, Sushma M. Bhosled, Dennis Liottae, Eric Hunterc, d, Fray F. Marshalla, Hinh Lyd, Ross J. Molinarod, Jerry L. Blackwellc, f and John A. Petrosa, b, d, Corresponding Author Contact Information, E-mail The Corresponding Author

a Department of Urology, Emory University School of Medicine, Atlanta, Georgia

b Atlanta Veterans Affairs Medical Center, Decatur, Georgia

c Yerkes National Primate Research Center, Emory Vaccine Center, Emory University, Atlanta, Georgia

d Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia

e Department of Chemistry, Emory University School of Medicine, Atlanta, Georgia

f Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia

Available online 3 April 2010.

Objectives

To develop a serum-based assay to detect 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 to identify patients with prostate cancer previously exposed to XMRV infection and those who carry XMRV viral sequences in their prostate.

Methods

Patients who had undergone radical prostatectomy were enrolled, and biologic specimens were obtained at surgery. 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.

Results

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.

Conclusions

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.

This work was supported in part by the Research Scholar Award to Hinh Ly by the American Cancer Society (grant Reprint requests: John A. Petros, M.D., Department of Urology, Emory University School of Medicine, 1365 Clifton Road, Building B, Atlanta, GA 30322
Urology Volume 75, Issue 4, April 2010, Pages 755-761

 

[MEKoan]

Thank you much, If!

 

[George]

I'd like to compare the two neutralizing assays, The one used in the Groom/Kerr paper and this one. Also, I wonder when the test is going to be available to the public?? Should we flood Emory University with requests for access to the test?? (big grins)

So are we all sitting around lapping up . . . I mean drinking our coffee this morning checkin' the web? (I'm working on my table manners so I can sit with the big dogs, I mean people some day. Grin)

 

[Kati]

It gets better and better... What a great Easter Week end!!!

 

[jimbob]

holy cow, what a monday after a tough weekend for me. two major stories!!!!!!!!!! hopefully this will get things moving quicker, as I am sooooo very impatient!

 

[Gerwyn]

I'd like to compare the two neutralizing assays, The one used in the Groom/Kerr paper and this one. Also, I wonder when the test is going to be available to the public?? Should we flood Emory University with requests for access to the test?? (big grins)

So are we all sitting around lapping up . . . I mean drinking our coffee this morning checkin' the web? (I'm working on my table manners so I can sit with the big dogs, I mean people some day. Grin)

PREVIOUSLY infected .The game is well and truly afoot

 

[George]

PREVIOUSLY infected .The game is well and truly afoot

Yeah, so when do you get tested Gerwyn?

 

[Gerwyn]

Yeah, so when do you get tested Gerwyn?

next tuesday

note patients who currently have DNA and those who by implication dont have a look at the methodology!

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.

 

[usedtobeperkytina]

Someone explain to me how seeing it in 11 of 40 who have the virus means it is a good assay.

Is my brain just not computing again?

Tina

 

[cfs since 1998]

Someone explain to me how seeing it in 11 of 40 who have the virus means it is a good assay.

Is my brain just not computing again?

"At a serum dilution of 1:150, our assay detected 11 (27.5%) of 40 patients with XMRV neutralizing antibodies"

I think they mean that they detected it in 11 patients out of the 40 patients tested, not out of 40 XMRV known positives. But I can see how you would interpret it that way because of the order of the sentence.

 

[George]

The results they got were the same results as the PCR and FISH. In other words according to PCR and FISH only 11 of 40 were infected. So the serological test was in concordance with the other results, therefore we win we made the test first.

I don't really get the "previous infection" wording part Gerwyn, I mean anybody infected was infected 'previously'. We're not talking about anybody who is being infected "currently" right???? So any infection is a 'previous infection' (head scratch)

 

[cfs since 1998]

I don't really get the "previous infection" wording part Gerwyn, I mean anybody infected was infected 'previously'. We're not talking about anybody who is being infected "currently" right???? So any infection is a 'previous infection' (head scratch)

It's because an antibody can't give you information on whether you are now infected, only that you were exposed at some point in time. When you are talking about a retrovirus though, it is usually assumed that an antibody = previous infection = current infection, since retroviruses can't be completely eliminated.

 

[George]

It's because an antibody can't give you information on whether you are now infected, only that you were exposed at some point in time. When you are talking about a retrovirus though, it is usually assumed that an antibody = previous infection = current infection, since retroviruses can't be completely eliminated.

Yeah, that's what I was trying to say (grins) what CFS articulated so well! Thanks

 

[Gerwyn]

Yeah, that's what I was trying to say (grins) what CFS articulated so well! Thanks

the key word there is assumed they could not find it in the dna or in the blood so where is it

 

[Gerwyn]

It's because an antibody can't give you information on whether you are now infected, only that you were exposed at some point in time. When you are talking about a retrovirus though, it is usually assumed that an antibody = previous infection = current infection, since retroviruses can't be completely eliminated.

yes i know but it is an assumption and not fact i would love to see the entire methodology .XMRV is the first human gamma.When the term retroviruses is used it is genericised usually referring to known human retros. we really dont know very much about xmrv so we are assuming a hell of a lot.

 

[Gerwyn]

The results they got were the same results as the PCR and FISH. In other words according to PCR and FISH only 11 of 40 were infected. So the serological test was in concordance with the other results, therefore we win we made the test first.

It is hopelessly written.I read it the other way.Anyway of finding the full methodology to confirm or otherwise?

Chronic infection, though, appeared largely limited to CD4+ T cells in lymphoid organs -- spleen, lymph nodes, and GI tract -- as well as in reproductive organs, including prostate, testes, ovaries, vagina, and cervix.

I don't really get the "previous infection" wording part Gerwyn, I mean anybody infected was infected 'previously'. We're not talking about anybody who is being infected "currently" right???? So any infection is a 'previous infection' (head scratch)

sorry my bit is mixed with yours above

We know about chronicity over a few months but the rest is anyones guess

Chronic infection, though, appeared largely limited to CD4+ T cells in lymphoid organs -- spleen, lymph nodes, and GI tract -- as well as in reproductive organs, including prostate, testes, ovaries, vagina, and cervix.

 

[citybug]

Someone explain to me how seeing it in 11 of 40 who have the virus means it is a good assay.

Is my brain just not computing again?

Tina

They don't expect it to be a high rate in prostate cancer. They think it is a subset. I think this is higher percentage than earlier study of prostate cancer.

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.

Does anyone know if this is part of the CFS type XMRV? Don't trust my ability to check Science paper. Is this an antibody test for CFS XMRV verified by another lab? WPI probably knew this was coming out.