Deja Vu in the UK XMRV CFS Study Negative Again!

UK researchers are not winning the hearts and minds of CFS patients thats for sure. Just a couple of uplifting weeks after Dr. Mikovits displayed so much enthusiasm and confidence in XMRV the other shoe has dropped. An Imperial College researcher said another negative study was coming and here it is; this UK study also failed to find virtually ANY evidence of XMRV in a large number of CFS patients. This study was similar and different from the Imperial College study.

Annette Whittemore said to be cognizant of whos doing the studies in this case, though, there doesnt appear to be any bias to question, no damning history of behavioral emphasis to reflect upon; two members of the study, Dr. Kerr and Dr. Gow, are long term ME/CFS researchers committed to a pathophysiological interpretation of this illness. (Ironically it was Dr. Gow that refuted Dr. DeFreitas finding 25 years ago).

Indeed, the paper went to some lengths to praise the Lombardi Science paper stating the apparently compelling evidence against the possibility of laboratory contamination and the immune response against XMRV the researchers demonstrated was present. They stated that they set out with the intention of confirming the Lombardi study.

PCR Tests
- This was a large study that looked at well over 500 CFS patients and controls from two cohorts in the UK and Scotland. They first looked for sequences on two the three genes XMRV possesses. When they didnt find anything the first time they looked again using a more sensitive assay.

Immune Tests - Unable to find evidence of XMRV by PCR they looked for signs that the patients immune systems were reacting to it. To do this they obtained some neutralizing antibodies against the env protein found in the family of mouse retroviruses. Antibodies neutralize retroviruses by attaching to them and preventing them from getting their hooks into cells. They also raise a red flag to the immune system to come and attack. As they examined this set of antibodies they were able to identify one that was specific for XMRV and they used it to search for the virus.

The neutralization test is a rather indirect one; they apparently add the antibodies to the sample and then (somehow) test the sample for infectivity. Since the antibodies attach themselves to the retroviruses the degree of infectivity should go down a certain amount and in a couple to test cases they confirmed this. When they ran the neutralizing antibody test on the 142 ME/CFS patients none of them met the criteria for infection. Ironically, 14% of the healthy controls from one of the healthy cohorts tested positive for infection, altho later testing suggested it was do to a different mouse virus.

They stated that they were confident that their PCR assay is more sensitive than the published single round PCR method and should have possessed the necessary sensitivity to find XMRV.

Two Different Tests : Two Different Results The WPI has backed away from the PCR test because of its inability to detect XMRV at very low levels and their associated lab VIP Dx is not longer offering it. This could not be a reason, of course, for the zero results seen in this test the WPIs PCR test may not be perfect but it appears to be able to find most instances of infection. We also know from Dr. Lombardi and from patient reports that the WPIs test IS finding XMRV infection in UK patients. Why they are finding it and two UK groups have not, is, of course, the big question. Either the patients are very different or the tests are. Since it seems unlikely that that the patients are THAT different its pretty clear that the WPIs test is quite different from these other groups.

Validation Not a Replication Study Its interesting, by the way, that this UK group with its ties to the WPI via Dr. Kerr did not appear to avail itself of the WPIs assays or or Dr. Singhs antibody tests. Since the group didnt appear to use the WPIs methods this is a validation study not a replication study; its was an attempt to validate the WPIs claim that theyd found XMRV not an attempt to determine if the the WPIs methods worked.

This is still just the beginning of the XMRV studies to come out but its a remarkable turnaround given the lengths the WPI, researchers from the NCI and the Cleveland Clinic went to in that compelling Science paper (Dr. Coffin called it as good a first paper as they get) to demonstrate the presence of XMRV. The fact they were able to show that this virus was able to infect previously uninfected cells and show a virus budding out of them still seems at least to this layman to be the most singular and important finding to date.

The Scientific Director of the CFIDS Association, Dr. Vernon, will reportedly release an analysis of the study tomorrow, giving us a much needed expert overview of the situation.

Comments

Thanks for the summary, Cort. If nothing else, these studies are keeping you busy! It will be good to hear what Dr. Vernon has to say. I wonder if WPI will have a response.
 
Thanks for the summary Cort. A bit of a rollercoaster. I'm glad Nancy Klimas warned us this is what it would be like, Orla
 
My understanding is that the WPI is now using Dr. Singh's antibody test specific to XMRV that shows INCREASED not decreased rates of positivity. It really is a conundrum; the WPI appears to be getting more and more internal evidence that they're right these papers are coming out suggesting that something went wrong. The first question always appears to be if what the WPI found is an endogenous retrovirus - a piece of junk DNA from an old mouse retrovirus in our genome. They sequenced 2 and a half strains of the virus and compared what they found against our entire genome against our entire genome and found nothing. Thats one of the reasons Science took the paper - they convinced them it was not an endogenous retrovirus.

I still don't see how they could be wrong. I think they've still done more to show that the virus is real than anyone has shown that its not. How could they be wrong? (How could they be right?) The twists in this story are amazing.
 
Bear in mind that we have yet to see a 'replication study'; no one has yet followed the WPI's study to the letter. Different groups are doing different kinds of PCR and different kinds of antibody tests. Theoretically they all should match up but they're not; the twists to this story are amazing and unsettling but the WPI has the National Cancer Institute and the Cleveland Clinic behind them; they produced 'the best' first paper possible and it landed in the most prestigous journal in the world. Other groups are doing more comprehensive analyses of the WPI results; Dr. Klimas said this was going to be an up and down process - she was clearly right!
 
Deja Vu , but without the same sense of outrage the first study engendered I think.

...IE: "What the %$#@'s Wessley doing messing with our stuff?!" induced outrage.

This study is just more bewildering.
I'm glad to have seen Klimas predict this too. It's taken the fright out of the ride! Somewhat :)
 

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