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CFIDS: THE ITERATION OF X (A breakdown of the Dr. Singh's Study)

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
It's getting boring to say the same thing again and again:

Ila Singh, prostate cancer: ~4% XMRV+ in healthy controls
Ila Singh, ME/CFS: 0% XMRV+ in 200 healthy controls

Explain this first, before you want to go look for other infectious agents.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
And another question:
The positive results from serological assays that indicate an immune system response to XMRV as reported in the Science paper have contributed to doubts about past negative papers. However, many experts, speaking at conferences and writing in the literature, have repeated the observation that Shin et al. make in the Journal of Virology, It is possible that assays that have found anti-XMRV reactivity in CFS patients are due to cross-reactivity to related antigens.
If those assays are cross-reactive, then to what have they reacted statistically significantly more often in ME/CFS samples than in those drawn from healthy controls? (I assume the serology results in Lombardi et al. were significantly different between cases and controls as well, if not, please show me, i can't access the paper.)
Have the investigators from Lombardi et al. contaminated their ME/CFS samples more often than the controls not only with XMRV or mouse DNA but also with antigens to some other, not yet identified virus, that by conincidence produces exactly the antibodies that can set off this assay?
 

Stone

Senior Member
Messages
371
Location
NC
Thank you, eric-s, for articulating my questions so well. I couldn't have said it better. If those patients with positive XMRV serology tests aren't cranking out an antibody response to XMRV but rather something else, then what would that be? Would/could this mystery agent also cause one to register positive on ELISA for Lyme but negative by western blot confirmation on repeated tests for Lyme over the years, as is the case with myself? Early on Dr. Mikovits was reporting (in several interviews) a fascinating high correlation between her XMRV positives and Lyme positives, to the tune of something like 40% if memory serves, but nothing's been published on that to my knowledge and I haven't heard much about that from WPI or Dr. Mikovits of late. What came of that? Anyone know?
 

LJS

Luke
Messages
213
Location
East Coast, USA
It's getting boring to say the same thing again and again:

Ila Singh, prostate cancer: ~4% XMRV+ in healthy controls
Ila Singh, ME/CFS: 0% XMRV+ in 200 healthy controls

Explain this first, before you want to go look for other infectious agents.

I believe in the prostate cancer study the positives in healthy controls was not blood samples but prostate samples from patients that had to have their prostates removed for other reasons. Singh is a great researcher, I do not understand why everyone has turned on her because she did not find XMRV. She is someone I would love to see continuing to study CFS.
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
I believe in the prostate cancer study the positives in healthy controls was not blood samples but prostate samples from patients that had to have their prostates removed for other reasons. Singh is a great researcher, I do not understand why everyone has turned on her because she did not find XMRV. She is someone I would love to see continuing to study CFS.

That's the point for me. In the monkey study, the blood of the monkeys who were infected with xmrv didn't always test positive for XMRV, but when they did autopsies they found the organs had a good deal of XMRV. Similarly, when she tested prostate tissue, controls were 4% positive; but when she only tested blood she found 0%. So how can she say flatly in the study and the title of the press release that XMRV is not associated with ME? I think the most she can say is that she didn't find xmrv in the blood of patients or controls.

eric, I am curious too, what are the antibodies reacting to, then? are 'they' claiming they're reacting simply to random mouse dna (or endogenous rvs in mouse dna) or do they acknowledge it could be another exogenous MLV?

I also wasn't thrilled at CAA's tenor of, oh well, XMRV's all over, but it generated some interest in ME so it was ok. I'm a layperson, but I think that's premature. The Singh study was informative, but didn't close the case. We don't know for sure either way.
 

LJS

Luke
Messages
213
Location
East Coast, USA
That's the point for me. In the monkey study, the blood of the monkeys who were infected with xmrv didn't always test positive for XMRV, but when they did autopsies they found the organs had a good deal of XMRV. Similarly, when she tested prostate tissue, controls were 4% positive; but when she only tested blood she found 0%. So how can she say flatly in the study and the title of the press release that XMRV is not associated with ME? I think the most she can say is that she didn't find xmrv in the blood of patients or controls.

I would be worried about that but the WPI continues to say they can find XMRV in the blood, I even tested positive through the VIPdx blood test, which the results seem to be almost random among CFS patients. Dr. Singh even tired to use WPI's test used in the Science study and was unable to find XMRV. Singh tried everything she could think of to try and find XMRV in the blood, nine different tests which all came up negative and she should know she has been studying XMRV for years. So to attack the study for not looking in other tissue when the WPI says it is present in blood is disingenuous.
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
It's getting boring to say the same thing again and again:

Ila Singh, prostate cancer: ~4% XMRV+ in healthy controls
Ila Singh, ME/CFS: 0% XMRV+ in 200 healthy controls

Explain this first, before you want to go look for other infectious agents.

Maybe XMRV lives in prostate tumor tissue and not in blood? Not saying it's true, just that it is one possible explanation. And they did say that in the macaques the virus persisted in tissue after it was no longer found in serum.
 

ixchelkali

Senior Member
Messages
1,107
Location
Long Beach, CA
And another question:

If those assays are cross-reactive, then to what have they reacted statistically significantly more often in ME/CFS samples than in those drawn from healthy controls? (I assume the serology results in Lombardi et al. were significantly different between cases and controls as well, if not, please show me, i can't access the paper.)

Good question. (And, yes, they found antigen reaction in ME/CFS samples but not in controls.) Even if it is a cross reaction, why the difference between ME/CFS patients and healthy controls?
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
I would be worried about that but the WPI continues to say they can find XMRV in the blood, I even tested positive through the VIPdx blood test, which the results seem to be almost random among CFS patients. Dr. Singh even tired to use WPI's test used in the Science study and was unable to find XMRV. Singh tried everything she could think of to try and find XMRV in the blood, nine different tests which all came up negative and she should know she has been studying XMRV for years. So to attack the study for not looking in other tissue when the WPI says it is present in blood is disingenuous.

I'm not saying she had to look at it in tissue in this study if she hadn't planned to do that, but how can she say that 'XMRV is not associated with CFS" just based on the blood? That seems disingenuous to me. Like I said, she should have just said she couldn't find it in ME blood. It's possible it's in tissues and not blood.

Apparently, one of WPI's positives they sent to Singh was one they used to grow a cell-line/strain from and they also took an electronmicrograph of XMRV coming out of a cell in this person's blood (in addition to finding it positive with some of the four or five tests WPI used). So it's possible that that sample is in fact positive and Singh couldn't find the XMRV. So, again, it's disingenuous to say "XMRV is not associated with ME" when we don't know that for sure. All we know for sure from her study is that she did not detect XMRV in any of the samples.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
I believe in the prostate cancer study the positives in healthy controls was not blood samples but prostate samples from patients that had to have their prostates removed for other reasons. Singh is a great researcher, I do not understand why everyone has turned on her because she did not find XMRV. She is someone I would love to see continuing to study CFS.
I didn't turn on her. I take this study seriously. But things don't add up. And before they do, i will not let this be.
Yes, that's exactly the point. In the other study they were not looking at blood.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
I would be worried about that but the WPI continues to say they can find XMRV in the blood, I even tested positive through the VIPdx blood test, which the results seem to be almost random among CFS patients. Dr. Singh even tired to use WPI's test used in the Science study and was unable to find XMRV. Singh tried everything she could think of to try and find XMRV in the blood, nine different tests which all came up negative and she should know she has been studying XMRV for years. So to attack the study for not looking in other tissue when the WPI says it is present in blood is disingenuous.
Just like i don't take this latest study by Dr. Singh as the last word, i don't take what the WPI says as being proven yet. For example, i don't call WPI positives "known" positives at this point. Not before they can correctly identify blinded samples provided by a third, trusted party.

Can you tell us more about the distribution of results from VIPDx's blood test? That would be interesting.

Like i said in the post before, at this moment things don't make sense. Before the picture makes sense, i think it would be just plain stupid to declare the case closed. It is possible the WPI are better able to find XMRV/MRV in the blood than Dr. Singh. And it is also possible there's no XMRV/MRV in the population at all. We have to find out.
If this latest study is correct, what is not possible, is that XMRV exists everywhere, at a low level, not associated with disease.

The WPI have said more than one time, i think, that the blood is not a good place to look for MRV.

If in the town where you live, a number of children have disappeared misteriously and there were signs that they could have been murdered and other signs that they could just have run away, but it was clear that it's not possible to say yet, which of both alternatives is true, because the signs are contradictory, would you let your 5 years old daughter go out and play alone at night?

I want to be sure what XMRV/MRV does.
 

LJS

Luke
Messages
213
Location
East Coast, USA
The WPI have said more than one time, i think, that the blood is not a good place to look for MRV.

I really do not think this is a valid argument. The WPI and patients can not just keep making excuses and changing the criteria for what is valid samples and tests when it is convenient. The WPI has made countless presentations and statements that they are able to find XMRV in blood with relative ease using multiple methods including straight PCR with no culture. I think it is clear at this point they are finding something but that something is not XMRV. If what they were finding was in fact XMRV then you would not have 26 negative studies. The WPI is probably using a test with too wide of a specificity and are picking up something else or a contaminate. There is no way to look at the data and conclude anything other then there is a astronomically high percentage that XMRV is not present in CFS patients. I really hope Dr. Mikovits can admit she made a mistake if and when she discovers it to try and save what little reputation they have left in the scientific community. I see that many patients will not accept XMRV is not present in CFS patients unless Dr. Mikovits says so.
 

urbantravels

disjecta membra
Messages
1,333
Location
Los Angeles, CA
Whatever happened to Dr. Singh's autopsy study???

I, too, would be very interested to know what is going on with that study. Unless my memory is scrambled (very possible) that one ought to have been done and published *before* this CFS study. But it's very possible that now *everything* she's been working on with regard to XMRV requires revisiting and possibly even retesting.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
The WPI have said more than one time, i think, that the blood is not a good place to look for MRV.

Yes, they have said that. But the original study that was published, was all about finding it in the blood.

http://www.sciencemag.org/content/326/5952/585.abstract

"Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome"



And perhaps the published conclusion needs to be repeated, as they chose their words carefully, which many of us have forgotten:

These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
I think it is clear at this point they are finding something but that something is not XMRV. If what they were finding was in fact XMRV then you would not have 26 negative studies. The WPI is probably using a test with too wide of a specificity and are picking up something else or a contaminate. There is no way to look at the data and conclude anything other then there is a astronomically high percentage that XMRV is not present in CFS patients.
I strongly disagree. This is your opinion, but i don't think it's a good interpretation of the facts. The studies concluding that there is no association between XMRV and ME/CFS were 0/0 studies. While it's really very hard to explain why there have been so many studies with this result (i don't know why), those studies have little credibility, as long as the prostate cancer studies are not discredited. Because they are contradicted by those. So i don't think they are a strong argument against the positive studies. Even though it might be true that Lombardi et al. and Lo et al. were wrong, i don't deny this possibility.

I also don't like everything the WPI has done and i also expect answers. And results, even more.

But it's not only them, who have said that XMRV is probably hard or at times even impossible to find in the blood. The macaque study concluded the same. So does the latest Switzer study.

Please don't evade and comment on the question that seems to be the most important one:
How can the 0/0 studies be valid, if the positive prostate cancer studies are not seen as wrong?
I don't think it's possible. So before those are proven to have been wrong, i don't see how you could use the 0/0 studies as arguments.
 

LJS

Luke
Messages
213
Location
East Coast, USA
Please don't evade and comment on the question that seems to be the most important one:
How can the 0/0 studies be valid, if the positive prostate cancer studies are not seen as wrong?
I don't think it's possible. So before those are proven to have been wrong, i don't see how you could use the 0/0 studies as arguments.

You can not prove a negative. It is like trying to prove the loch ness monster does not exist, it can not be done. So scientist are doing what they can do, try everything they can think of to find XMRV with basically no positive repeatable results. Only a few of the prostate studies found XMRV just like a few blood studies but serious questions have be raised about some of that data. I can go and look it up but it was published and discussed here earlier that some of the techniques used to find XMRV in prostate cancer are highly susceptible to contamination.

Everything in science is based on repeatability, if something is not repeatable there is a huge problem. Some seriously smart and competent people have given XMRV everything they got and come up empty. So it is basically up to the WPI at this point to prove themselves which I feel they have been doing a terrible job at. Instead of reaching out to scientist Dr. Mikovits as just been attacking them. Instead of being cool and collected in response to serious questions she as been emotional. Instead of inviting those that disagree with her into her lab to show her what she is finding she jumps from one excuses to another why they can not find it and states that her work has no issues, all science has room for improvement including her work. How the whole thing is being handled is incredibly frustrating to me, the science paper was a perfect moment for the CFS community to come together and try and draw more researcher in, instead I feel the statements from the WPI and patients of throwing everyone under the bus that disagrees with them is just doing the opposite.
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
I strongly disagree. This is your opinion, but i don't think it's a good interpretation of the facts. The studies concluding that there is no association between XMRV and ME/CFS were 0/0 studies. While it's really very hard to explain why there have been so many studies with this result (i don't know why), those studies have little credibility, as long as the prostate cancer studies are not discredited. Because they are contradicted by those. So i don't think they are a strong argument against the positive studies. Even though it might be true that Lombardi et al. and Lo et al. were wrong, i don't deny this possibility.

I also don't like everything the WPI has done and i also expect answers. And results, even more.

But it's not only them, who have said that XMRV is probably hard or at times even impossible to find in the blood. The macaque study concluded the same. So does the latest Switzer study.

Please don't evade and comment on the question that seems to be the most important one:
How can the 0/0 studies be valid, if the positive prostate cancer studies are not seen as wrong?
I don't think it's possible. So before those are proven to have been wrong, i don't see how you could use the 0/0 studies as arguments.

I agree........