XMRV CFS UK study #II

[Orla]

No problem Katie. I was just getting the post up quick and had meant to just highlight that Kerr was collaborating with the WPI elsewhere and so not the situation with McClure (where I think there was no contact with the WPI).

I don't think the Mikovits/Kerr grant was necessarily for XMRV (though possibly it could be used for that) so I am not sure that it is certain that there will be a joint XMRV study from them anytime soon. However maybe they will use some of the money for it?

Koan, I don't think anyone won't read further as it is imposible not to be curious! But I did mention the discussions and also the MRC press release which implies they don't think the story is fully over either.

Ronan thanks for the info. Another European study would be good.

Orla

 

[usedtobeperkytina]

Adam, if you are still reading, take this to heart...

Cleveland Clinic and National Cancer Institute are with WPI results and put their name to that study. These are two very reputable institutes. They didn't make it up.

Science journal is the highest in editorial rigor. They had very high demands for WPI, NCI and CC to meet before publication.

Secondly, Mikovitz has said this virus is very tricky, popping in and out, being active then dormant and hiding.

This study also says that XMRV is infectious in humans. This validates the new discovery made by the WPI. No one had seen that before.

Also, WPI is reporting that 50% of the people they test, not the ones in the study, have XMRV. Now, if their science wasn't based on the evidence, then wouldn't they be stating a higher number to add more validity? The answer is that even with their tests (I mean VIP), it is hard to detect.

Also, realize that Defreitas saw something also. She saw it at a higher rate in CFS patients. It isn't a figment of WPI and Defrietas.

Maybe CFS is caused by multiple retroviruses, different ones in different patients. All of which have not been discovered except XMRV and Defreitas' study. Maybe there are, say 10 different human infectious retroviruses, all of which can cause DNA / immune system abnormalities that leads to CFS. Maybe this is just the beginning of the discovery into these. Remember, it wasn't too long ago that the human genes were mapped out. Do they know a lot about all of these genes, or which of them are retroviruses or which of those retroviruses cause illness and which are benign? There is a lot of cancer out there... and they don't know what causes much of it. Could it be a large number of yet to be discovered retroviruses? What I have read about NK Cells is science doesn't fully understand them. Local GPs don't even consider them in tests or treatment or as a cause of illness. When I mention NK Cells to doctors, they dismiss it because they don't know enough to address it.

When my mother was diagnosed with breast cancer at the age of 49, she asked what was the cause. Doctor said, "environment, genetics, viruses, chemicals, food we eat.... we don't know.) After all the money that has gone into breast cancer research, and they still don't know.

So don't think, Adam, that this one study shuts the door on XMRV, or another retrovirus, from causing CFS.

Tina

 

[ukme]

I'm feeling so gutted but hanging in there; if it's not XMRV the WPI will keep searching and we need to stick with them and stick together

 

[usedtobeperkytina]

And by the way, as was said, this is a rollercoaster ride.

The joy of the ride is the ups and downs. We had some ups, and now we have some downs, time to go back up. We had a study that showed in vitro that XMRV his hindered when androgens are limited. That was an up.

Not every Christmas present you open is what you wanted. So let's just ride it out. Don't be discouraged, enjoy the ride.

Also, as far as I am concerned, I am glad we have something to talk about. And thanks to WPI, we got some attention from scientists and some research going on. For a while, all we were talking about was how sick or how better we were and how awful Wessely and Reeves are.

Tina

 

[usedtobeperkytina]

by the way

And by the way, as was said, this is a rollercoaster ride.

The joy of the ride is the ups and downs. We had some ups, and now we have some downs, time to go back up. We had a study that showed in vitro that XMRV his hindered when androgens are limited. That was an up.

Not every Christmas present you open is what you wanted. So let's just ride it out. Don't be discouraged, enjoy the ride.

Also, as far as I am concerned, I am glad we have something to talk about. And thanks to WPI, we got some attention from scientists and some research going on. For a while, all we were talking about was how sick or how better we were and how awful Wessely and Reeves are.

Tina

 

[julius]

I'm only half way through the thread so sorry if this is already discussed. But I want to ask this before our science wizards go to bed.

Could this be a case of XMRV-1 in North America and XMRV-2 in Europe?

 

[dmarie4301]

Maybe the prevalence of XMRV is more prominent in the US? Maybe ME in the UK is a completely different disease process than CFS in the US. Many people believe they are 2 separate illnesses, maybe they're right. Just as HIV started in Africa and spread globally, perhaps XMRV has not made its way to that part of the UK. Maybe there is more than one retrovirus that can cause the same constellation of symptoms. There can be a hundred different reasons why the study has not been replicated in the UK at this time. I think these findings are very preliminary, and so much more research has to be done. Our symptoms mimic SO MANY other disease processes, it's really hard to narrow it down and figure out who has what.

But many UK people have been tested through VIP and are positive. Some PCR, moreso the culture. XMRV exists in the UK

 

[Gerwyn]

Why do you think they used the controls they did answer they would find endogenous gammas in this group that would give them positive serotype reactions and apparently validate their assay technique no one uses seriously ill people as healthy controls

 

[spindrift]

Just been speaking with a lab in Belgium who are going to be replicating the WPI study using the exact same techniques as the WPI. They were over in Reno last week to get a better idea of the techniques being used. They have seen this latest report and their repsonse to me 5 mins ago was this is more of a reason why the want to replicate the WPI results as soon as possible. Its all confusing at the moment, even for us who are following it closely. Earlier today i was of the thinking that it was the beginning of the end for XMRV and CFS but now im not so sure. The rollercoaster continues!

Thanks for the post. Do you have any idea what " as soon as possible" might mean in this case?

 

[Mithriel]

Past my bed time but I have been trying to make sense of this. Thanks Gerwyn and George, I get very confused by the technical details.

ME and Incline Village CFS are probably the same disease, but CFS as we have in the UK covers all sorts of things some of them purely psychological.

I've gone over it again and this is a summary of who they tested and what they found.

St Georges London gave them 142 samples from clinics all over England. None of these tested positive by PCR or had antibodies to XMRV. These clinics only take ambulatory patients and people on forums have said that staff show surprise when someone with typical ME symptoms comes in as they are sicker than the usual patient.

They also had samples from 157 blood donors none of which were positive by PCR but 14.4% were positive by neutralisation. Most of these came from one blood donor session so they are flummoxed by that.

From Bart's, they had 226 samples of blood from sick people. None of these were positive by PCR but 1.3% were positive by neutralisation.

They then tested 28 patients and 12 controls from Glasgow for antibody and one patient was positive, but no controls.

Glasgow is where some of the classic work on ME was done. Behan husband and wife did very good work with Eleanor Bell and then Chaudray(sp?) was there too. John Gow worked here but may have moved. he has done some good work, but I felt he was too dismissive of a lot of stuff, too quick to say that something couldn't be. He has never been psychosocial school at all though. He disproved Elaine de Freitas work and the Coxsackie B work, though in that case I did not think his findings were very persuasive.

All lab work is challenging especially until it is properly worked out. It is very difficult to grow bacteria in the lab and they have been doing that for 150 years Viruses are much more difficult and PCR is very technical. In my OH's lab they had real trouble with a test that had always worked before. It turned out that the urine samples were being collected in paper containers instead of tin ones and something in the recycled paper inhibited PCR.

PCR works best on the appropriate sample. That may well be why XMRV was detected more easily from cancerous tissue than CFS can be from blood. Maybe PCR would be best in, say, T cells.

Dr Bell said there would be many negative studies before the positive ones. Every new organism has its own foibles and XMRV is different from other human retroviruses.

Mithriel

 

[flex]

XMRV "Present or not in UK"

Just a point about different strains of XMRV possibly not being present in the UK and this accounting for zero findings in UK tests - lets remember that a number of Europeans including Brits who sent their blood to the WPI tested positive for XMRV.

 

[kurt]

The huge variable in this study is the age of the bloodIn the "cfs" group the sampling began in 2003 and "preserved" .In the control group the blood from "healthy" volunteers was about a year old on average.The conclusions of the study could just as easily have read that" xmrv can be detected in fresh blood but not in "old" blood this could be explained that the viruses in old blood were much less viable in old blood "" PCr would be unlikely to work as it needs rapidly replicating viruses".alternatively as the prevelence of xmrv titre was much greater in healthy controls than cfs patients we must question the quality of the blood supplied by cfs patients . Unless you control variables you cannot reach the conclusions of these authors without at least highlighting this possibility.I haven,t read the rest in any detail but the science falls at the first hurdle!

Why is age of blood an issue? WPI found XMRV in 25 year old samples. Yes WPI re-ran their samples many times (which they did not report initially), but by your reasoning they should not have had positives (unless it was some type of HERV reaction they actually found in those old samples?). Anyway, if WPI did get XMRV positives from old blood, they should have had some hits even on the first run, and so Kerr should have gotten some positives in this study. Also, this study was able to get hits on a known positive as well as carefully spiked positives. That says their test worked at least to some degree.

Also, they required 16 antigen copies? Didn't the IC study work with 1 single copy? Interesting, this was a less sensitive PCR test than the IC study.

but only using the "serology" test. They ended up with 26 positives, 1 from a CFS patient and 25 from the healthy controls, then they narrowed this down to only 4 because they set the "serology" test up to pick up a kind of wide range of things, what is up with that???

The serology (antibody) testing is for MuLV and not specific to XMRV. Even activated HERVs can produce a positive. Using serology and saying that proves something is a bit of a dodge. So now people are believing serology tests are specific for XMRV, but that is wrong. Serology is supportive only and not conclusive.

XMRV clone sequence deleted and substituted in the env region---completely different drom other VP62 clones is this really xmrv clone at all monoclonal antibody response not specific to xmrv what virus did they find prize for the best answer!

What virus indeed. My guess is that WPI has found a novel MuLV type retrovirus or a HERV, and not XMRV at all, so as replication/validation testing gets more and more specific for XMRV they will have less and less success. That is probably why only serology testing is working. Or possibly serology is picking up a HERV expressed in CFS (which also could include RT). Some smart lab who sequences the antigen will figure this out. Also, note that neither Kerr nor WPI used the pol gene, why are they avoiding the stable portion of the genome?

Cant wait for the powers to be....the ones we are trusting....to respond to this study.

Who are you waiting for? This is science, there are no 'powers to be', certainly not WPI, they are disqualified scientifically from confirming their own finding, and are biased in any response to outside efforts. These collaborating labs ARE the powers you are waiting for, and this IS the evidence for or against XMRV that we are waiting for. The score right now is not looking good for XMRV in CFS.

There is still good research going on right now in the CFS community and some promising leads for other explanations. XMRV is not the only game in town.

Just been speaking with a lab in Belgium who are going to be replicating the WPI study using the exact same techniques as the WPI. They were over in Reno last week to get a better idea of the techniques being used. They have seen this latest report and their repsonse to me 5 mins ago was this is more of a reason why the want to replicate the WPI results as soon as possible. Its all confusing at the moment, even for us who are following it closely. Earlier today i was of the thinking that it was the beginning of the end for XMRV and CFS but now im not so sure. The rollercoaster continues!

Their interest in replicating has nothing to do with what they will find. If XMRV was a false finding, the Belgian study will likely also not find any XMRV in CFS. The final outcome is still unknown by ANYONE, we just have to wait.

I will take a cup of Chamomile, read a good book, and continue trying to be objective and not to get too emotionally involved in this process, it takes years sometimes.

 

[Ronan]

Thanks for the post. Do you have any idea what " as soon as possible" might mean in this case?

In a couple of weeks all going well they will be able to do the Culture test. They are also sending some serum samples to them in the next week or so for a serology assay.

 

[julius]

originally posted by Kurt;

"What virus indeed. My guess is that WPI has found a novel MuLV type retrovirus or a HERV, and not XMRV at all, so as replication/validation testing gets more and more specific for XMRV they will have less and less success. That is probably why only serology testing is working. Or possibly serology is picking up a HERV expressed in CFS (which also could include RT). Some smart lab who sequences the antigen will figure this out. Also, note that neither Kerr nor WPI used the pol gene, why are they avoiding the stable portion of the genome?"


So Kurt, if this hypothesis is correct, then WPI would have found something in 98% of PWC and 4% of healthy controls. Am I understanding that correctly.

That would be fine with me. It would still be a significant finding, poiniting (probably) to a causal factor, or at least a biomarker. So the task over the next while will be to identify what that something is. If it's not XMRV who cares. A biomarker is a biomarker.

 

[ukxmrv]

Ronan,

Do you mean Redlabs? I heard that they had licensed the test from the WPI

 

[Katie]

originally posted by Kurt;

"What virus indeed. My guess is that WPI has found a novel MuLV type retrovirus or a HERV, and not XMRV at all, so as replication/validation testing gets more and more specific for XMRV they will have less and less success. That is probably why only serology testing is working. Or possibly serology is picking up a HERV expressed in CFS (which also could include RT). Some smart lab who sequences the antigen will figure this out. Also, note that neither Kerr nor WPI used the pol gene, why are they avoiding the stable portion of the genome?"


So Kurt, if this hypothesis is correct, then WPI would have found something in 98% of PWC and 4% of healthy controls. Am I understanding that correctly.

That would be fine with me. It would still be a significant finding, poiniting (probably) to a causal factor, or at least a biomarker. So the task over the next while will be to identify what that something is. If it's not XMRV who cares. A biomarker is a biomarker.

I like your way of thinking Julius! Maybe another breed of retrovirus? I'd be interested to read Kurt's thought on this.

 

[cfs since 1998]

What virus indeed. My guess is that WPI has found a novel MuLV type retrovirus or a HERV, and not XMRV at all, so as replication/validation testing gets more and more specific for XMRV they will have less and less success. That is probably why only serology testing is working. Or possibly serology is picking up a HERV expressed in CFS (which also could include RT). Some smart lab who sequences the antigen will figure this out. Also, note that neither Kerr nor WPI used the pol gene, why are they avoiding the stable portion of the genome?

The score right now is not looking good for XMRV in CFS.

I will take a cup of Chamomile, read a good book, and continue trying to be objective and not to get too emotionally involved in this process, it takes years sometimes.

An HERV that can infect other cells?

WPI sequenced virus from patient samples differed by six nucleotides from an XMRV strain found in prostate cancer. This is less than the difference between two different XMRV prostate cancer strains. How is that a completely different virus let alone an HERV?

You say the score is not looking good based on studies that can't find XMRV in ONE SINGLE SAMPLE and use spiked controls rather than an actual patient control?

Claiming you are objective does not make it so.

 

[starryeyes]

These UK studies have come out too quickly to be of any use to anyone. They're sure jumping the gun to try to disprove the findings of the National Cancer Institute, the Cleveland Clinic and the WPI. That wouldn't be because they have an agenda to continue psychologizing ME would it?

The only thing I don't understand is why would Kerr be mixed up with these "researchers"?

Thank you to those that have shined a light on the truth of the matter here. I'm looking forward to the results from the real studies. :sofa:

 

[Jimk]

If you read the Mikovits lecture transcript, she makes it clear that PCR alone will fail to detect the virus... even if they used the same protein sequences which they did not... without amplifying the signal by concentration through cell culture. Even then only 68% detected (99% only later when they added the serology). In other words, not only is the patient population selection important as many have been discussing here, but methodology is critical with this bug. A retrovirus not in replication will show few proteins to be detected.

I made the same comment at this posting of the research: http://7thspace.com/headlines/33521...tients_with_chronic_fatigue_syndrome.html#cst
"This study did not replicate the Mikovits et al one in Science, and used a single PCR (on a different protein at that) rather than the three step method used in the Science study: PCR amplified by cell culture, antibody and infecting uninfected cells to validate. The headline "Absence of XMRV in UK" is completely misleading. More accurate might be "Study designed to be unable to detect XMRV in UK." "

 

[ukxmrv]

Jimk,

Do you mean "replicating cells with LNCaP co-culture for 5 days prior to PCR" which is something I've got jotted down from one of the WPI talks.

I've been through the Gow paper this afternoon and cannot find any reference to it but could be mistaken.