Cooperative Diagnostics PCR Test Poll For an ACTIVE Infection

What is the Result of Your Cooperative Diagnostics PCR Test?

  • I have severe ME/CFS: I tested positive

    Votes: 0 0.0%
  • I have moderate to severe ME/CFS: I tested positive

    Votes: 1 8.3%
  • I have mild to moderate ME/CFS: I tested positive

    Votes: 0 0.0%
  • I have mild ME/CFS: I tested positive

    Votes: 0 0.0%
  • I have severe ME/CFS: I tested negative

    Votes: 3 25.0%
  • I have moderate to severe ME/CFS: I tested negative

    Votes: 7 58.3%
  • I have mild to moderate ME/CFS: I tested negative

    Votes: 1 8.3%
  • I have mild ME/CFS: I tested negative

    Votes: 0 0.0%

  • Total voters
    12

kurt

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Hi Kurt. I was just pointing out that when you say it's just as likely that the WPI was mistaken, that also means the NCI and the Cleveland Clinic being mistaken, which is true.

Kurt said:
people here are acting like XMRV is an established fact so any lab that does not find it in 'my CFS' is obviously flawed, but that is just not the case.
I don't think that's a fair characterization of the very thoughtful examination of information that goes on on this forum.
fresh_eyes,
You are right, I should have said 'some people here..'. There are many viewpoints represented here.

But I think you have to admit that the thoughtful examination tends to be very one-sided. How many people here are carefully examining the Science article objectively? Maybe we need a thread for that.
 

fresh_eyes

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How many people here are carefully examining the Science article objectively? Maybe we need a thread for that.
You know, I think that's an excellent idea. I'd like to read a well-thought-out, substantive critique, written by people who know CFS is a real, disabling illness - especially if it didn't have an argumentative tone, which I find frustrating and difficult to wade through at times. It would help all of us understand where good scientists might, in good faith, take issue with the WPI's results.

I don't think it's working well to critique the study on these poll threads, among people who are themselves in the midst of the highly-charged process of getting tested.
 

spit

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A thread devoted to critique on the actual study would be good, I think, especially here where people aren't trying to minimize each other's illness at all. I can reread it in a while and see what comments I might have, both critical and positive -- a few of each come to mind -- but I'm not sure I have the brainpower this afternoon, sadly.

I personally find it a very significant study, though it's still far too early to view it as an answer. I think overall that they did a great job of dotting their t's and crossing their i's, or what have you. There are still reasons it might not pan out as either correlated so widely with CFS or causal to it, and those are probably worth exploring in a really honest way among friends.

The overarching thing, to me, is that until it's replicated and the assays are well validated, testing is in a muddy area both in terms of accuracy and in terms of meaning. That's not to say I think nobody should get tested, and I can see reasons people might want to do so, just that the "what now" of either positive or negative results is totally up in the air and will be for at least some months. That's worth keeping in mind before, during, and after testing, and is probably the only major caveat that I think people in these particular results threads should really take to heart.

Well, and also that we're not a scientific sample. So please don't view the results here as more than interesting, because they're not controlled the way one would control actual data.

Otherwise, I have to agree that these threads are really for people who have results and want to discuss those; getting either result has emotional meaning even if the physical meaning is still unclear, IMO, and I suspect that we've all heard all of the caveats, too. It's hard work, balancing hope with the unknown when you're sick.
 
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Also, antibody testing for MuLV is problematic, there have been studies that show cross-reactivity, it is a problematic test. So XMRV in CFS comes down to PCR evidence
Yes, XMRV can be serologically cross-reactive with SFFV, as well as some other retroviral entity that I forget. But few or no normals have the antibodies according to the Mikovits paper. Flat wrong is the contention that only PCR evidence remains.

Evidence from cross-reactive antibodies is not meant to show with certainty that XMRV is present. XMRV merely is very likely to be the virus detected, because it has been reported from humans and the cross-reacting agents havent been.

The antibody-based evidence that it is XMRV remains strong enough to bolster the strong evidence from PCR + sequencing. Which, to repeat, is gold-standard stuff, from which it is maximally difficult to get a false positive. And the possibility of PCR contaminated with the target sequence remains -- but this danger exists in the same degree with all variants of PCR.

In short, suppose you find PCR positivity to some bacterium in 67% of people with CFS, and this agent is uncommon in normals but has reported in humans before. What are the odds that, additionally, 95% of them (Mikovits' unpublished figure) are seropositive for two bacterial proteins that could only come from some small set of bacteria including the one you found by PCR+sequencing. These odds are very low. Thus, the PCR+seq results make very formidable evidence when combined with the three types of antibody-based assays found in the paper. The two arms of the paper are mutually reinforcing.

Nonetheless, for various reasons, I will revise my odds that XMRV causes CFS from 80% down to 67%.
 

acer2000

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But few or no normals have the antibodies according to the Mikovits paper.
I'm curious about this. They are quoted in the media as stating their "expanded" set of test (aka not the ones the used in the paper) found 95% PWC tested had this virus. But I have never seen the figure that said what the % of controls went up to after they used the expanded set of test - or if they even tested more controls. Does anyone have this information?
 

kurt

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Yes, XMRV can be serologically cross-reactive with SFFV, as well as some other retroviral entity that I forget. But few or no normals have the antibodies according to the Mikovits paper. Flat wrong is the contention that only PCR evidence remains.
I believe that other retroviral entity is HERV family retroviruses. They often interfere with antibody testing, particularly for MuLV. There are hundreds of studies reported that have attempted to find retroviral cause for various diseases and many reports of false positive antibody studies.

Also PWC have more activated HERVs than normals, probably due to HHV infections (which trigger HERVs), so that could explain a higher rates of false positives on MuLV antibody testing. I am not saying that is what happened, I have no idea what WPI really found, but just want to point out that there is precedent for exactly this type of problem in this type of study. Here is a huge review of the literature of retrovirus hunting problems, often due to HERVs. If you have access to this article, it is a must-read for this type of issue:

Human RNA "rumor" viruses: the search for novel human retroviruses in chronic disease.

Also, which Mikovits paper do you refer to that reports testing of controls for antibodies? I am not familiar with that. The Lombardi et al article in 'Science' did not mention that, at least not that I could find.
 

rebecca1995

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We really can't judge the Cooperative Diagnostics data until it is peer-reviewed and published. Their failure to detect XMRV might be due to something like leaving the samples sitting out too long.

Happy New Year, everybody!
 
C

Cloud

Guest
To the best of my understanding, the "Viral Culture DNA" (XND1 with VIP) test would completely rule out false positives. You can't grow something that's not there. I suppose one could still get a false negative with this test, but it reduces those odds.
 
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re HERVs -- touche. Definitely a serious possibility -- if there is something in the human genome that can cross-react with any/all of the antibodies used.
 

garcia

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Nonetheless, for various reasons, I will revise my odds that XMRV causes CFS from 80% down to 67%.
Interesting, personally I'm revising my odds that XMRV causes CFS up from 50% to 67%. Also I note that there are now 9 out of 9 negatives for the CD test. Caveat Emptor!
 

kurt

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To the best of my understanding, the "Viral Culture DNA" (XND1 with VIP) test would completely rule out false positives. You can't grow something that's not there. I suppose one could still get a false negative with this test, but it reduces those odds.
The viral cultures are reportedly tested using WB, which is an antibody test. So if antibody testing is giving false positives, then all that is proven in a culture is that the lab can grow whatever bug is giving the false positive. So unfortunately, no, culture testing does not rule out false positive.
 
C

Cloud

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Thanks Kurt...I didn't realize that. Have you heard of any other non xmrv pathogens giving false positives with this culture test? I guess the PCR tests solve that diagnostic problem anyhow.
 

Kati

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I see that everyone so far that is on this forum and that has taken the poll for Cooperative Diagnosis tested negative... Anybody finds this worrisome? That's now 10 of them...
 
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What he means is that it "reads out" using antibodies. These are not patient antibodies, but rather ones stocked by the lab which are generally from rabbits, goats, whatever. They stick to XMRV and (in at least some cases) to related entities. They have a "fluorophore" attached which emits visible light when energized with UV light. So, if XMRV gets from the patient sample into the "bait" cells that are uninfected when the assays starts, you detect it by lighting it up using these brightly fluorescing antibodies.

You can make goat antibody against anything you want. All ya gotta do is jab it into a goat a few times appropriate intervals.
 
C

Cloud

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I see that everyone so far that is on this forum and that has taken the poll for Cooperative Diagnosis tested negative... Anybody finds this worrisome? That's now 10 of them...
Yep, it's concerning that if put side by side, the CD and VIP labs are turning out very different results. The implications beyond just the obvious seem worthy of inquiry.
 

kurt

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Thanks Kurt...I didn't realize that. Have you heard of any other non xmrv pathogens giving false positives with this culture test? I guess the PCR tests solve that diagnostic problem anyhow.
The research literature has shown that false positives with that antibody study are common. So yes, there are other non-xmrv pathogens that will show positive with the MuLV antibody and culture tests used in the Science study. In my opinion that was an omission of the Science article, to not include references to that possible confound. This omission has contributed to an overly positive presentation of their study.

I see that everyone so far that is on this forum and that has taken the poll for Cooperative Diagnosis tested negative... Anybody finds this worrisome? That's now 10 of them...
Not worrisome at all, if you accept the many statements by WPI that XMRV could turn out to not be a factor in CFS. The problem is that many people (not all) have focused only on the idea that XMRV will be the cause of CFS and are ignoring the warnings, even those by WPI.

I remember when I first learned about Lyme Disease. I so hoped I had just Lyme Disease, and not CFS. So I got tested, got treated several different ways. Eventually I realized that people with Lyme had abilities that I did not, many can still exercise for example, and that I had CFS and not just Lyme. I guess that just shows how desperate we are for an explanation, and a solution. So for me, the CD poll means I should listen to WPI's warning, and realize that XMRV may not be what people had hoped.

The viral culture test is not an antibody test. The antibody test is not available yet.
What he means is that it "reads out" using antibodies. These are not patient antibodies, but rather ones stocked by the lab which are generally from rabbits, goats, whatever. They stick to XMRV and (in at least some cases) to related entities. They have a "fluorophore" attached which emits visible light when energized with UV light. So, if XMRV gets from the patient sample into the "bait" cells that are uninfected when the assays starts, you detect it by lighting it up using these brightly fluorescing antibodies.

You can make goat antibody against anything you want. All ya gotta do is jab it into a goat a few times appropriate intervals.
Exactly. And those antibodies are known to stick to a range of MuLV type infections and also HERVs.

Yep, it's concerning that if put side by side, the CD and VIP labs are turning out very different results. The implications beyond just the obvious seem worthy of inquiry.
CD and VIP are not that far apart, considering how early we are still in the science. VIP seems to be having many fewer positives than the statistics from the WPI study would indicate. And which direction are they actually heading? The positives seem to not be increasing as fast as the negatives.

http://www.midlandsbiz.com/articles/4289/
Well, there have to be at least 2 XMRV positives using the test, right? What about the 2 friends with CFS that inspired Brent C. Satterfield, Ph.D., President and Founder of Cooperative Diagnostics, LLC. to come up with the XMRV test in 16 days. He did check it on them. Didn't he? Kurt?

Makes me wonder about the possibility of all the macho guys in Guatamala bragging to the senoritas that they are HIV negative:
CD has a 100% reliability on their XMRV test. Dr Satterfield is a biomedical engineer, he helped the Dept of Homeland Security with anthrax testing, and he has developed tests for many govt agencies, including internationally. CD specializes in rapid test development, they could do that already before XMRV. The level of incompetence you are assuming just does not fly with the facts here. Of course there is a chance the CD test is totally inaccurate, but I think the odds are very small. An alternate scenario is that there was a problem with the WPI PCR study, and their antibody and culture tests hit on the high level of HERVs in PWC rather than on XMRV. Also, the samples they sequenced might have been real positives from lymphoma patients, after all that is how they found XMRV, by studying CFS Lymphoma samples.

So it is possible the CD results do not show XMRV because it simply is not there very often. If XMRV were there they would probably find it, as they do in known positive prostate cancer samples (they can find a single antigen cell in a small sample, that is as good as it gets). Some replication studies are finding the same thing, no XMRV in PWC. This scenario has happened before, in retroviral hunts in other diseases. I think WPI knew that, and so they tried to warn us, but at the same time they needed support for their new center, so they have been walking a fine line. I hope they resolve this soon, they have to realize by now something is wrong. They are in a double bind. If replication studies are failing because WPI did not explain completely how they run their tests then they will look bad and researchers will not trust them. On the other hand if the replication studies are failing because XMRV is simply not there, they will look over-eager, like they published too soon. I think the second scenario is better for WPI, and understandable for a new research group in a difficult economy, so I hope that XMRV is actually not there and this is just an artifact of the scientific method. Then we can see what else WPI has to offer, such as explaining the interesting findings of their virachip study. Anyway, time will tell all...
 

Kati

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I remember when I first learned about Lyme Disease. I so hoped I had just Lyme Disease, and not CFS. So I got tested, got treated several different ways. Eventually I realized that people with Lyme had abilities that I did not, many can still exercise for example, and that I had CFS and not just Lyme. I guess that just shows how desperate we are for an explanation, and a solution. So for me, the CD poll means I should listen to WPI's warning, and realize that XMRV may not be what people had hoped.
Kurt I am sending my blood to Igenex tomorrow for Lyme testing and honestly I'd rather not have lyme, because canadian doctors think that Lyme disease stops at the border- they think it's not prevalent in Canada. Therefore the treatments are difficult to get, usually underground. Visiting the Lyme websites, it sounds like the symptoms are very much overlapping and similar to CFS/ME and it's concerning to me. I also understand that the Lyme test, even western blots are not totally definitive and some doctors treat with antiiotics with only clinical signs of the disease.

What a nightmare and what a big mess.
 

Kati

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If this test is so good at detecting XMRV in prostate cancer, then why have they not marketed it for prostate cancer patients? Surely that would be a broader market; much more profitable. Cancer patients will want to know their XMRV status too, because it is associated with the more aggressive forms of cancer and would be a diagnostic for the type of treatment needed.

Whoops! I guess that test would need to be FDA approved, and certified by government review as reliable by adequate research and documentation. Can't get that done in only 16 days . . .

Levi, I am not sure cancer patients are aware there is a retrovirus lurking on them in the same way than the CFS/ME population is aware of it. For one thing, they got an aggressive cancer- which means very likely it has already spread, usually to the bones. Then it's already too late. In my opinion, while it is interesting to know the link between prostate cancer and XMRV, there will be a need to screen patients BEFORE they get the diagnosis, and it sounds like studies are already happening for women with cervical cancer (Cancer Institute?)
 

Kati

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Ladybug, I hope she didn't tell them- and please keep us posted about the results... Looking forward to it.