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Failure to detect XMRV-specific antibodies in the plasma of CFS patients

Jemal

Senior Member
Messages
1,031
Another negative 0/0 XMRV paper, by Tufts (where Coffin resides) and Abbott Diagnostics. The same people worked on other negative studies as well.

Failure to detect XMRV-specific antibodies in the plasma of CFS patients using Highly Sensitive Chemiluminescence Immunoassays
Brendan Oakes, Xiaoxing Qiu, Susan Levine, J. Hackett Jr., and Brigitte Huber
Received 8 April 2011; Accepted 10 June 2011

Academic Editor: Myra McClure

In 2009, Lombardi et al. reported their startling finding that the gammaretrovirus xenotropic murine leukemia virus?related retrovirus (XMRV) is present in 67% of blood samples of patients suffering from chronic fatigue syndrome (CFS), as opposed to only 3.7% of samples from healthy individuals. However, we and others could not confirm these results, using a nested PCR assay. An alternative to this highly sensitive, but contamination?prone, technique is to measure the serological response to XMRV. Thus, we tested the plasma samples from our cohorts of CFS patients and healthy controls for the presence of XMRV?specific antibodies. Using two novel chemiluminescence immunoassays (CMIAs), we show that none of our samples have any XMRV?reactive antibodies. Taken together with our previous findings, we conclude that XMRV is not present in any human individual tested by us, regardless of CFS or healthy
control.

http://www.hindawi.com/journals/av/aip/854540/

Don't have the energy to go through this paper, so I don't know if it brings anything new to the table.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
How many more of those do they want to produce? I mean i really wonder, instead of working for months and months, i would just make a call and say "Hey Judy, can i drop by and you show me how you do it?". They could then still make up their own minds wheter what they see is correct or not, but i'm just having a hard time understanding why people go about this problem by trying to develop their own methods instead of looking at the method that is reported to be successful. Once you have done that, you could then still, in a further step, develop another, better, method if you're capable of doing so.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
This is a continuation of a previous negative study in which they failed to detect the virus. In this study they look for antibodies.

Conclusion:
With the serological data added to our original finding, we can unequivocally conclude
that XMRV is not present in our CFS patient or healthy control cohort samples. Although we
have detected XMRV gag sequences in three of our samples, they all tested positive for mouse
DNA and tested negative for XMRV specific antibodies.


All the authors, except one, are from Tufts University or Abbott Diagnostics.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
Is it good practice for scientists to use that kind of wording, "unequivocally conclude"? It's a serious question, i would like to know if this is seen often or they only do that here. If it's not the usual thing it might be more interesting than the actual content of the paper.
 

Daffodil

Senior Member
Messages
5,875
well....we know beiger's study will be positive. ugh. would be so nice if they would look for a virus instead of spending so much money and time - time we do not have - just trying to prove wpi wrong. must be nice to have the luxury to engage in a pissing contect while people are dying.
 

kday

Senior Member
Messages
369
Bias:
With the serological data added to our original finding, we can unequivocally conclude that XMRV is not present in our CFS patient or healthy control cohort samples. Although we have detected XMRV gag sequences in three of our samples, they all tested positive for mouse DNA and tested negative for XMRV specific antibodies.

Unbiased:
With the serological data added to our original finding, we [STRIKE]can unequivocally[/STRIKE] conclude that XMRV [STRIKE]is not present[/STRIKE] was not detected in our CFS patients or healthy controls [STRIKE]cohort samples[/STRIKE]. Although we have detected XMRV gag sequences in three of our samples, they all tested positive for mouse DNA and tested negative for XMRV specific antibodies.

Who reviewed this?
 

kday

Senior Member
Messages
369
Wow, I just read the whole thing and I can rip that piece to shreds. Bias and factual errors are present everywhere. Amazing.

Is Hindawi pay-to-publish or are humans just blind? Whoever has the energy should take these pieces and correct all the errors to embarrass the authors and reviewers.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Maybe we should start a sarcastic "Correct this study thread" where, with full attribution to the original article, we correct their conclusions? That might drive the point home, particular if we wind up with hundreds of corrected studies on it. Bye, Alex
 

kday

Senior Member
Messages
369
Maybe we should start a sarcastic "Correct this study thread" where, with full attribution to the original article, we correct their conclusions? That might drive the point home, particular if we wind up with hundreds of corrected studies on it. Bye, Alex

I think something like this could keep science quite fair. I think there are too many attacks on researchers, and this is unnecessary in my opinion. Also, personal attacks are not effective.

The truth is, researchers do read these forums as evident by some of their statements.

I think they would be more careful about what is published when they see their journals are published with errors. We don't need to change or manipulate data (unless it's completely misrepresented), all we need to do is prove these studies lack neutrality.

And we can do media blasts just like them. It's possible.

Imagine the headline:

"CFS Patients Fight Back by Correcting Errors and Bias in Research Papers"
 

ukxmrv

Senior Member
Messages
4,413
Location
London
What do you mean by media blasts and headlines Kday? I've been sending press releases and trying to get UK reporters interested in this for a while now. Have had no success. Even we we organise demos and patient actions in the UK they won't report it in papers.

The playing field isn't level and hence patients feel frustrated. It may be that the internet is one of the few ways we can make a difference here.
 

omerbasket

Senior Member
Messages
510
How many more of those do they want to produce? I mean i really wonder, instead of working for months and months, i would just make a call and say "Hey Judy, can i drop by and you show me how you do it?". They could then still make up their own minds wheter what they see is correct or not, but i'm just having a hard time understanding why people go about this problem by trying to develop their own methods instead of looking at the method that is reported to be successful. Once you have done that, you could then still, in a further step, develop another, better, method if you're capable of doing so.
I want to stergthen you words. They are saying that their assay was excellent in rhesus macaques. Well, that's a way to try and develope assays for humans, but this is not a validated test for humans and we don't know if it has any value in diagnosting human beings. It can be that it has, and it can be that it hasn't. Not every test that is good in macaques is also good in humans.
Now, to date, the only serological tests that is known to have found evidence for a gammaretrovirus in a (large, considering VIP Dx's tests) group of humans is the tests performed by the WPI Lombardi et al. 2009 methods. It must be used by others, as this is what is called "replication" - a basic scientific procedure. After using these assays, if they would find evidence for a gammaretrovirus, they can still argue that the results are misleading and that those persons, found to be positive by these tests, never had a gammaretrovirus. Ofcourse, they must add their arguments, to explain why they think so. They can also add tests that would strengthen their statement, and perhaps they can even prove it to be correct. But unless they prove it with 100% certainty to be correct (that these serologic tests are giving false results), than the debate about this must be proceeded, as long as there are scientists who think otherwise.
To date, almost nobody have presented arguments that tried to deal with "why the WPI/NCI found antibodies to a gammaretrovirus that is not there (according to many of the scientists that performed the negative studies)". Coffin said that this could be even F-MLV, and it is not specific for XMRV. The WPI never argued that it's specific to XMRV - they said that it proves that those people are infected with a gammaretrovirus, but never said that the serological testing proves that they were infected with XMRV. They did, however, said that finding XMRV in their body (by PCR, transmission electron microscopy etc.), not finding any mouse mtDNA though checking the samples and reagents for that, showing the phylogenetic tree, and finding gammaretrovirus-antibodies in some of those patients - shows that there was XMRV in some of those patients. But they didn't say that the antibodies were specific just to XMRV - they said that they were specific to a gammaretrovirus. In fact, Dr. Mikovits talked about a patient that was negative for XMRV by PCR, but positive for the serology test - and later on they found a PMRV in her. I think that it is actually the same virus, just with a mutation - but there is some sequence difference there, ofcourse.
So that's what's need to be done - to replicate the WPI methods, and if you have positive results but you believe that they are false positives (for a gammaretrovirus - nobody said that these antibodies are specific for XMRV - they said that they are specific for gammaretroviruses), you should explain why - and the other scientists should decide what they believe, and should try to prove it.

Now, as to why in he current study they didn't use the WPI/NCI methods for the serology test: To me it looks pretty much obvious. I think that the reason for that is that Abbot took part in this study and in the assay deigning. Now, Abbot is a commercial company, and potentially they could have two reasons for doing what they have done:
1) The more probable reason, in my opinion: They really wanted to find antibodies for XMRV, but they only had an interest to find those antibodies IF THEY WOULD FIND IT WITH A TEST OF THEIR OWN. That is because ONE CANNOT REGISTER A PATENT THAT IS ALREADY REGISTERED (and I think that the WPI and NCI already applied for a patent regarding their testing for XMRV and serological testing for a gammaretrovirus). Now, that aspect can also be about other studies, whether or not they include commercial companies among their authors. People might say that this may reflect also on the WPI/NCI - I doubt it, since at the end there won't be testing (at least in humans) for a retrovirus that would not be proven to be in humans, and therefore nobody would try to still their invention if their invention produced only false positives.
Anyway, in this case, Abbout was honest about its inability to find positives - but if this option is correct, they did not perform the best study that they could, and they did so because they had no financial interest in performing the best study that they could (and it's also possible that they had a financial interest in not showing that the WPI/NCI methods can find antibodies for a gammaretrovirus in humans).
2) The less probable option, in my opinion: Abbot are arfraid from a possibility that one of their products directly or indirectly got those people to be infected with XMRV/a gammaretrovirus. If this is true, than they would probably have a big interest in making the XMRV/HMRV thing go away as soon as possible. In my opinion, however, this is much less probable than option number one.
 

omerbasket

Senior Member
Messages
510
I think something like this could keep science quite fair. I think there are too many attacks on researchers, and this is unnecessary in my opinion. Also, personal attacks are not effective.

The truth is, researchers do read these forums as evident by some of their statements.

I think they would be more careful about what is published when they see their journals are published with errors. We don't need to change or manipulate data (unless it's completely misrepresented), all we need to do is prove these studies lack neutrality.

And we can do media blasts just like them. It's possible.

Imagine the headline:

"CFS Patients Fight Back by Correcting Errors and Bias in Research Papers"
I also thionk that it would be a good idea. Many of the conclusions drawn in those studies are very premature, are not proven by the studies, and lack the voice of the opposite side (which has excellent, world-known scientists in it - and isn't it enough to say "Robert Silverman, Francis Ruscetti and Harvey Alter"?).
 

*GG*

senior member
Messages
6,389
Location
Concord, NH
I also thionk that it would be a good idea. Many of the conclusions drawn in those studies are very premature, are not proven by the studies, and lack the voice of the opposite side (which has excellent, world-known scientists in it - and isn't it enough to say "Robert Silverman, Francis Ruscetti and Harvey Alter"?).

I think this is good idea also, we are being noticed, and what does it say about these researchers and PUBLISHERS when sickly patients can find "big" errors with their articles/data?!

I don't see how respectable researchers and publishers can present papers in which errors can be easily found?

GG