German study finds xmrv

[omerbasket]

Thanks for that nice analysis Dr. Yes.

What a huge find - somebody actually finds XMRV! Sweet. And apparently using different methods than the WPI - that just makes it sweeter (and the XMRV finding stronger).

My guess is that there isn't a problem about it being an opportunistic virus. I actually think this strengthens XMRV case in CFS. That depends on how immuno suppressed these patients are vis--vis chronic fatigue syndrome patients. We talk all about the immune problems in CFS but it is true that a number of immune abnormalities that consistently show up in CFS are not that large; there's RNase L (which the research world has ignored) and NK cell problems and some others but its nothing like immune problems that show up in AIDS. Some researchers on our side talk about mild immune dysfunction - they're not really impressed by the degree of immune dysfunction in all. Others think the dysfunction is much more problematic.

In any case could the immune dysfunction be six times worse than the immunocompromised patients? I wouldn't think so. Then why is it apparently showing up in such large large amounts in CFS patients and in such smaller amounts in patients the medical profession in general really does consider immunocompromised?

An opportunistic virus wouldn't do that. A virus that somehow targeted CFS patients would however.

I think the gap is too large to say that XMRV just 'tagged onto' CFS. I think based on this that XMRV is still a special problem for CFS patients and that it just happens to be in immune compromised patients (along with whatever other pathogens they have) - as well.

If they'd found it in 60 or 70% of those patients maybe we'd have a problem but when it's still so much more prevalent in CFS I don't think we have a problem. It does make things more interesting...and just shows how interested in XMRV researchers are - they're looking for it all over the place and hopefully we'll have many more studies coming out and we'll have to work through each one of them.

For me the big news is that someone found it - and that means (unless they made some weird mistake) that the three negative studies are history......

You know what? Now that I think about it - The 3 negative studies about ME/CFS and XMRV tested all together 388 patients who they claim have CFS, and found XMRV in non of them. Now, This study we have here founds XMRV, in Europe (although not in the UK or Holland), in 6 people out of 168 (3.6%), 2 of them are healthy and any of them are not immunosupressed (and in addition they found XMRV in 16 patients out of 161 who are immunosupressed). Now,is that just me, or is it very much unlikely that people with ME/CFS would be resistant for XMRV os oppose to people who does not have ME/CFS (which is also called Chronic Fatigue and Immune Dysfunction syndrome), one third of them are healthy people and none of them are immunocompromised?
To me, it says that it is very very very likely, that these 3 negative studies didn't find XMRV because their methods were not able to find it, or because they really wanted not to find it. That is, because I find it hard to believe that people with ME/CFS have such a good immune system that they would be even much less susceptible for XMRV infection than healthy people (I mean, 388 ME/CFS patients with no XMRV infection in any of them, and 62 healthy people that 2 of them are infected with XMRV and that is just by PCR testing of BAL and throat swab).

 

[bluebell]

bluebell ive been doing this for years you know, they cant find a cause so ive looked far and wide for a reason, everything from ice cream to (i dont drink milk ) to chemicals in the enviroment. i suspect a lot have played this guessing game. want to know a cause so bad i guess, over to the experts. thats it im shush.probably not helping sorry everyone

Hey Free,

I didn't mean to discount your experience or ideas. I have done the same thing, messed with diet, vitamins, etc. Who knows what they will discover, but it would be nice if it were simple, even if it's scary-simple.

This study doesn't give us what we need, but it does effectively put us back to the first day after the Science paper came out by showing that the negative studies were rubbish. Even if there are other factors, at least we have the hope that if we can take care of the XMRV we can all jog and smoke pot again (I prefer a nice glass of wine). I did not mean to sound dismissive - just wanted to point out that, as I understand it, XMRV could be the whole answer for many of us. Take good care.

 

[Esther12]

I'm looking forward to being a plague carrier.

That's quite a step up in social status for a CFS patient.

I've gone back to this study, and the numbers of patients involved are quite low. It's still a good sign that XMRV is in the general population (yipee!), and that the zero XMRV studies got something wrong, but the percentages involved could have been altered massively by chance, and I don't think we should see this as doing much to back up the WPI's figures yet.

As the paper involved those who'd previously failed to detect XMRV it would be really interesting to hear them explain why they thought they got such different results.

 

[eric_s]

I wouldn't worry too much about the social status of XMRV positive people. This is to be expected to be in around 2 to 4 percent of the population and it might have been there for decades. Noone has taken measures to prevent it's spread until now, and yet it did not affect a higher percentage of the population, so it can't be so easy to transmit. And most of the people who have it seem to be fine, so i don't think it has such a high potential to scare people.

 

[IamME]

sorry but this doesn't make sense. I'm xmrv+ and sick since birth. My mother has had symptoms too since young age, but no cfs and certainly no prostate cancer!
I know you are just speculating, but there are a lot of xmrv+ onthe forums. Suggesting that their loved ones will all get sick is not something you should do when you dont have evidence for that.

Look if you don't like the suggestion that XMRV is an infectious disease causing pathogen then don't read threads/research about it. I'm not the one who brought up transmission through saliva or coughing! Or lymphoma or any of the other bad news we're used to. Of course it's speculation, but a lot of this is, I thought that was the point of this thread, to discuss and speculate? And only when the general population realise that they *are* at risk will any real money be put into researching this. That's what happened with AIDS -- no-one gave a monkeys when it was "just a gay thing". Yeah it sucks, well, so does my "life" and I'm guessing yours isn't a bed of roses either. So lets not tip toe around it.
If you got sick from an early age that ties in with my paraphrasing JM on "vertical transmission" meaning you could have been infected since birth (when your immune system was more vulnerable so why you got sick sooner), and if your mother had symptoms she's at least partly affected by it rather than being simply a carrier. I myself have a sudden onset of disabling ME but preceded by odd symptoms for many years. I don't lknow what else to say. If you have a better theory, spill. The alternative to me is to say that XMRV is not the "big bad" but just another opportunist, which will if that's shown, give the psychs a shot in the arm. A pathogen that is supposed to be the cause yet only provokes disease in a modest % and even worse, is said to causes more than one otherwise unrelated disease seems on shaky ground. If you really want to know I'm not 100% convinced that XMRV is the "big bad" yet, but it's hoovering up a lot of virus attention so I'm going to give it some cautious support until something better.

 

[starryeyes]

Parvo wrote: A potential hiccup in the transfusion studies being developed in the US: If they only look for XMRV in the donor and recipient blood, they may be missing the "Second Strike" part of the equation. When investigating whether ME/CFS can be transmitted by blood products, shouldn't they look for BOTH strikes? Shouldn't they also look for ALL the opportunistic viruses which might hypothetically activate a latent XMRV infection? Too tired to finesse this - but this really needs to be followed up on. Thoughts anyone?

I've been thinking along these lines. They still need to find DeFreitas's CAV again too as that is another retrovirus that was found in us.

Since it sounds like XMRV is being found in other illnesses maybe you need XMRV and CAV to end up with ME/CFS. Once they find CAV again they should be testing for it in these other illnesses that share many overlapping symptoms with ME/CFS.

 

[Gerwyn]

I wouldn't worry too much about the social status of XMRV positive people. This is to be expected to be in around 2 to 4 percent of the population and it might have been there for decades. Noone has taken measures to prevent it's spread until now, and yet it did not affect a higher percentage of the population, so it can't be so easy to transmit. And most of the people who have it seem to be fine, so i don't think it has such a high potential to scare people.

4% of the population is in the USA amounts to millions of people.All known gammaretroviruses are oncoviruses(cause cancer)If XMRV does not cause cancer it will be the only gammaretrovirus in history that does not!.They may seem to be fine but are they? bearing in mind that gammaretroviruses are vertically transmitted a 4% polulation prevelence is frightening especially given that Polytopic Mulv viruses cause neurodegenerative diseases in mammals. if this one does not then once again it will be the only one not to do.just because they don,t have ME does not mean that they will not go on to have MS or altzheimers like other mammals with neurotoxic Mulv infections all do
gammaretroviruse are gene manipulators.This could do virtually anything!

 

[Gerwyn]

Why do we think this paper used different methods to the WPI? I see thta one is looking at blood and the other at saliva but maybe the PCR is the same?

The original WPI science paper says:
"we isolated nucleic acids from PBMCs and assayed the samples for XMRV gag sequences by nested PCR (5, 6). Of the 101 CFS samples analyzed, 68 (67%) contained XMRV gag sequence"
If you look, reference no. 5 is to the Urisman paper that is also referenced in the German study under discussion in this thread. Reference no. 6 of the WPI paper is to their own supplementary materials that say "Nested RT-PCR for gag sequences was done as described (5)". Again in the supplement the Science article refers to, I assume, the PCR from the Urisman paper.

If you look up the original Urisman paper (free access - http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020025#ppat-0020025-sd002) and look at the supporting material download "Protocol S2. XMRV gag Nested RT-PCR", it describes a nested GAG PCR. Is this the one under discussion? Looks to me like this is the one used in the Fischer study we are discussing. I note also that Fischer is one of the authors listed the Urisman study.

Like others here this study looks like great news, but I am wondering if they have found it precisely because they used the same PCR test as the WPI? If so then it seems to me that this is not an issue of blood vs. saliva so much as demonstrating the difference between testing methods. If I have interpreted this correctly (I realise I might not have) then maybe this is more of a true replication study, in testing terms, than any of the others even though they were using saliva and not blood?

Are any of you more scientific types able to shed more light on these thoughts?

It is not the question of PCR they looked in the right place amplified their sample ,cultured to raise the titre and then used PCR.In short they followed the instructions

 

[IamME]

I didn't make any reference to "loved ones" anyway, I was referring to the 2-4% of people apparently infected with XMRV which the WPI have said they think (though it's not technically proven yet) is disease-causing (which means it *will* cause disease, the only question how much and how soon).

Perhaps some people who are worried about their non-pwME family should consider for a moment that some sufferers don't have family, don't have kids, will probably never have a family, a relatonship, or any of these normal things, because of having severe ME/CFS.

 

[bullybeef]

4% of the population is in the USA amounts to millions of people.All known gammaretroviruses are oncoviruses(cause cancer)If XMRV does not cause cancer it will be the only gammaretrovirus in history that does not!.They may seem to be fine but are they? bearing in mind that gammaretroviruses are vertically transmitted a 4% polulation prevelence is frightening especially given that Polytopic Mulv viruses cause neurodegenerative diseases in mammals. if this one does not then once again it will be the only one not to do.just because they don,t have ME does not mean that they will not go on to have MS or altzheimers like other mammals with neurotoxic Mulv infections all do
gammaretroviruse are gene manipulators.This could do virtually anything!

That is fascinating, Gerwyn, because for some reason, I really wouldn't be surprised if XMRV is linked to umpteen diseases and disorders, none of which were previously linked, and they [the researchers] are going to spend an awful lot of time to confirm what you have just said in a few sentences.

Understanding that HIV/AIDS can cause dementia, is a big issue, because with all these dementia concerns of the modern era, and people just blaming it on life expectancy increases, is just biting the bullet. Something always causes something, and things like environmental factors may not help, but they're not the cause. Why can't people understand the simple process of cause and effect. Could a retrovirus [XMRV?] be causing something like dementia too? We all know about cognitive dysfunction in ME, don‘t we?

 

[Gerwyn]

Your analysis implicitly assumes that the CFS ==> XMRV infection; this is not at all established, and looks less likely all the time (see post #64 above).

A gammaretoviral infection explains the entire symptom complex of ME

 

[Sam Carter]

Hi fellow travellers,

....

(Does anyone know if FMS trigger points correspond to lymph nodes?)

...

Bye
Alex Young

Not necessarily, Alex.

 

[garcia]

This study doesn't give us what we need, but it does effectively put us back to the first day after the Science paper came out by showing that the negative studies were rubbish.

Good analysis.

 

[Gerwyn]

The scary implication is what is happening to the immune system of people with CFS. Think about it. There is an increased incidence of 7% of XMRV between people taking drugs to surpress their immune system over the health controls. In the original WPI study in science the number of CFS patients with it was 65% (or there about, too lazy to look). They then said it was actually higher.

That means if you have CFS your immune system is more trashed than a group on immune surpressing drugs. That should get someone's attention...

In ME the IMMUNOMODULATION is caused by the virus in the immunosuppressed people it is caused by the drugs big difference! SO the logic does not follow

 

[garcia]

I was referring to the 2-4% of people apparently infected with XMRV which the WPI have said they think ... is disease-causing (which means it *will* cause disease, the only question how much and how soon).

There seems to be some confusion here. Disease causing doesn't mean it *will* cause disease, only that it *can* cause disease. There are plenty of disease causing pathogens which produce little or no symptoms in most/many people (e.g. typhoid, Chlamydia, EBV, herpes etc). Indeed everyone harbours disease causing organisms, albeit not normally an exogenous retrovirus. Even HIV doesn't always cause disease as some people seem to be carriers but are immune to the effects.

 

[Impish]

In ME the IMMUNOMODULATION is caused by the virus in the immunosuppressed people it is caused by the drugs big difference! SO the logic does not follow

I don't think you read my follow up. The point I was trying to make (poorly in the first post) was that regardless of everything else the fact that so many people with CFS have XMRV clearly points to a physical cause for CFS. Given the % results of XMRV in "normal" and those on immunosuppressed drugs when compared to CFS patients finally at long last takes away the "it's in your head" arguement. Even if you don't think XMRV causes CFS the fact that the patients are full of a virus shows that something is wrong. You don't give CBT and graduated exercise to people whose primary problem is physical. Bye bye Weaselly and the millions of dollars that have been wasted down a blind alley.

 

[Gerwyn]

I'm toast, but here's a few observations...

This study looked in respiratory secretions, not in blood, so it is somewhat surprising to see the same kind of percentages the WPI found. That suggests the possibility that XMRV can easily migrate to any tissues well-supplied by blood. An alternative possiblity would be that XMRV shows a specific tropism towards the lungs.

Important points:

- These researchers did not use the same techniques as the WPI.

- They found XMRV in the respiratory secretions of people with diagnosed or suspected respiratory tract infections [three groups: organ or bone marrow transplant recipients (9.9%), people who had recently travelled by air (2.3%), and people with COPD and suspected respiratory tract infections (3.2%)] and in healthy controls (3.2%).

- As noted above, the control group showed a percentage of XMRV positivity similar to that found in controls by the WPI and Japanese XMRV studies

- Except for those who had travelled by air, the people sampled were known to be from northern Germany. (I don't think we know where the transplant material came from, though).

- The transplant (immunosuppressed) group had an XMRV positivity rate about three times higher than the control group's at the 90% confidence level (but not at the 95% confidence level).

- 10 of the 16 XMRV-positive samples from the transplant group (immunosuppressed) showed no sign of coinfection, despite tests for a variety of viral, bacterial, and fungal pathogens. (Raising the question of what exactly was causing their severe RTI.. it could of course have been one of any number of other pathogens besides XMRV that were not tested for, but...)

- From the study: "Attempts to isolate infectious virus from XMRV sequence–positive respiratory samples failed, possibly because of inadequate storage of samples before virus culturing attempts or relatively low copy numbers of the virus within the samples. Thus, whether the respiratory tract serves as a putative transmission route for XMRV cannot be determined at this time."

In other words they found XMRV sequences in these samples, but cannot say more than that. The percentages in all but the immunosuppressed group are the same or lower as the control group, so there is no evidence of transmission via respiratory secretions. (The 'travel' group had higher percentages of common RTI pathogens like influenza than XMRV.)

- The researchers double-checked the validity of their PCR findings by testing six samples (3+, 3-; I assume the latter were all controls) with two alternative assays.

- One sample out of those six, when tested for type C reverse transcription activity, showed a high level of activity. This suggested an active XMRV infection, but the authors noted that this is not the most sensitive assay around.
--------------------------

We can't draw conclusions yet about what this says about the transmission nor the role of XMRV in any of these cases (though the absence of coinfections in 10 of the 16 positive transplant patients is potentially interesting). The higher rate in the transplant group suggests that XMRV - like other viruses - takes advantage of the kind of immunosuppression transplant recipients undergo.

they did use the same techniques Doc. there is lymphoid tissue in the lungs.T and B cells are lymphoid.The WPI looked in B and T cells.In old blo0d they would not have been replicating.That is the reason for the apparently complex methodology.The Germans went straight forthe lymphoid tissue in the lungs where the virus would have been replicating anyway(all mulv class viruses replicate in lymphoid tissue).They key however even at these relatively huge titres they still had to culture the sample to find XMRV by pcr!

 

[Sam Carter]

It's worth pointing out (if someone hasn't already!) that if the prevalence of XMRV in the general population is approx 4% that would make it about 40 times more prevalent than HIV. Given the potential / likely pathogenicity of XMRV this makes it an enormous public health concern.

 

[Gerwyn]

Couldn't it also mean that XMRV was transmitted to them in the transplanted tissue?

Advocate

the point is that xmrv is an oncovirus immunosuppression will bring xmrv out of latency so the other way of considering the data is not that immunosuppression caused an XMRV infection but that there was a higher rate of XMRV present in the first place! this does not behave like other viruses!

 

[Gerwyn]

Hi villagelife

No they were just looking for XMRV in respiratory secretions, and a good source of respiratory secretions for a study are stored samples taken from patients with respiratory tract infections (diagnosed or suspected). Only one of the three RTI groups clearly had weak immune systems (the transplant group). They did not establish whether or not XMRV is a passenger virus in these patients, and even if it was that has little relevance to ME/CFS. In the case of ME/CFS, if the WPI's unpublished numbers are correct, I highly doubt that it is an innocent bystander.

dont forget that XMRV is an oncovirus hence there is a higher chance that it was present in higher numbers of people given immunosuppresant drugs in the first place