Article on the Spanish XMRV studies

[eric_s]

Hi all

Here's a Spanish article on the studies done in Badalona (Cataluna, Spain) that were presented on the 1st International Workshop on XMRV.

This is the link to the article

And here's a translation done with Google

Preliminary results of tests on the research team XMRV retrovirus Can Ruti

Lidia Monterde
League SFC / Rebellion

Summary of trials XMRV in Spain, presented earlier this month in the first international meeting of researchers on the retrovirus XMRV in Washington DC

Earlier this month in Washington DC, held the first international meeting of researchers on XMRV retrovirus, which is involved in the Chronic Fatigue Syndrome (CFS) and other diseases. Before the meeting had been published studies showing the relationship between XMRV and CFS (published in Science and PNAS Lombardi group and the recent study by the NIH and FDA). At the Washington meeting were presented studies that had also found this relationship, studies by Dr Paul Cheney, Dr. Kenny De Meirlaen, Dr Bell and the Catalan team of "Can Ruti (IrsiCaixa Foundation, Hospital Germans Trias i Pujol Badalona). The three papers presented by the team of Can Ruti are on pages 25, 26 and 35 of the report in English of the meeting:

http://regist2.virology-education.com/abstractbook/2010_8.pdf

Although the immunology and virology are complex issues, we make a summary of these trials. (Thanks to all healthcare professionals who collaborate with us on this issue to our website).

YES, HE HAS FOUND "the bug"

The main thing so far, tests of Can Ruti is that XMRV has been detected in patients with CFS in some patients with HIV and in some healthy controls. This detection was carried out as a pilot study with a small number of people because the objective at this point is not so much a study of prevalence but find out which are the first two steps to detect this retrovirus. And thanks to these tests, you can say it has succeeded in establishing the first steps to detect this retrovirus that presents a great difficulty in their detection.

Combining the three methodologies used in these tests for the detection of retrovirus could add up in CFS patients possibly between 36% and 72%, which is in line with published studies in the U.S. although the team Can Ruti percentages do not enter it probably not statistically significant in a small sample. That is why it plans to expand the study with a larger sample in the near future as reported by press.

In any case the most important of these three tests can be summarized as follows:

- The XMRV retrovirus is present in patients with Chronic Fatigue Syndrome Spanish.

- The XMRV retrovirus is also present in the healthy population in Spain and in patients with HIV.

- The mechanism of pathogenicity of XMRV must be elucidated in vitro studies, but data collected in the study suggest that B cells may represent a reservoir for retrovirus XMRV and contribute to its pathogenicity. The data also show that the histological study of human lymphoid tissue is a suitable model for analyzing the pathogenesis of XMRV.

- Studies of B cells, T and NK cells suggests a global immune dysfunction of unknown cause as a potential contributor to the mechanism of development of CFS. NK cells showed a significant decrease in the expression of CD57 +, and observed high levels of CD69 and activation of cytotoxic receptor NKp44 and NKp30 Nkp46.

- After 14 days of culture, the cells of the tissues were very positive, confirming that the XMRV fragment was able to infect the tissue of the tonsils in the absence of external stimuli.

TEST FOR TEST

(Translation and summary of Jose Luis R)

TEST 1 (page 25 of report) "Detection of XMRV sequences in EBV-Transformed B cell lines." Authors: J White, J Carrillo, E Garca, J Areal, Clotet B, C Cabrera.

About 21 cell lines for 11 CFS patients, 5 healthy controls, four patients with HIV and one with prostate cancer tissue obtained by PCR amplified genes ENV, GAG and POL (these are the three genes that make up the XMRV) the following results:

ENV: 4 positive, 21 of which 3 with SFC, a healthy
GAG: 3 positive on 21 of them, an SFC, a healthy, HIV 1
POL: Positive on July 14, including 4 SFC, two healthy, HIV 1

With a sample so small it is difficult to know the percentage of affected but could be located, possibly in 72% of patients with Chronic Fatigue Syndrome.

On the other hand we observed the effectiveness of XMRV to infect in vitro and in vivo lymphocyte cells such as B lymphocytes

As a new, state that Epstein Barr virus act as a "gateway" of XMRV within B cells that act as "reservoir" (the place where most viruses accumulate) of disease

Our preliminary considerations:

1 .- It is very important that a reference laboratory as IrsiCaixa retrovirology retrovirus has been detected in patients with Chronic Fatigue Syndrome in a rate, if confirmed, could easily dovetail with those published so far by the WPI (67%) and PNA's (just over 80%).

2 .- It is the first time in Europe XMRV detects the presence of not only patients but in healthy people and people with immune problems (such as people with HIV).

3 .- The B lymphocytes to act as a possible reservoir of the disease would note the difficulty of finding copies of XMRV blood and support the Rituximab and similar tests that cause a transient improvement of the disease by causing the destruction of certain B lymphocytes (CD19).

4.-Although it would be desirable to have percentages of the results but being a pilot is not as important as the rates that you were able to find the XMRV and begin to determine their performance. We imagine now that it has detected will be extended, as if that seems to claim, IrsiCaixa trials.

TEST 2 (page 26 of report): "Xenotropic murine leukemia virus-related lymphoid tissue Infection in ex vivo human." Authors: C. Cabrera, M Curriu, J Carrillo, M Massanella, Garcia E, Clotet B, C Carrato, J White.

In this paper we attempt to show whether the XMRV can infect lymphoid tissue based on the evidence of infection and replication in rhesus macaques XMRV.

This is done XMRV cultivation of tonsil tissue causing the infection at 7 days and 14 days after superinfection.

Despite the infection, counts are conducted on different B and T lymphocytes and their number almost corresponds to that of uninfected tissue.

In conclusion the study shows that the virus can infect lymphoid cells in vivo but does not cause a reaction or inmumolgica or kills them.

Our preliminary considerations:

1.-The first thing that has proven again (as was done in animal models) that the virus has a great ability to infect different tissues, in this case lymphoid tissue from tonsil cell culture.

2.-The study stresses that there is no difference in amount of B and T lymphocytes from infected cells and healthy cells XMRV.

3.-There seems to be enough evidence to believe that the XMRV infects lymphocytes, but unlike HIV, it kills them. This would cause it to be very difficult to detect in plasma-replicating copies the virus stays in their reservoirs of B-lymphocytes and distort the quantitative analytical ie the number of B and T lymphocytes would be the same as in healthy people, with the difference that functionality would be diminished, and last difficult because treatment is replicated and expose little bit in the plasma, at least theoretically.

TEST 3 (page 35 of report) "Altered B, T and NK cell phenotype in chronic fatigue syndrome (CFS) individuals". Authors: M Curiu, Massanella M, Carrillo J, Puig J, Rigau J, Clotet B, C Cabrera, C White.

This essay seeks to establish a differential immunopathologic pattern among people with CFS and healthy people.

Participants: 12 volunteers CFS and 15 healthy volunteers.

The aim is to establish the phenotype (external form) of B cells, T and NK cells and characterize their cytotoxic activity (attack) and their level of spontaneous apoptosis (natural self-destruction).

Conclusion:

It is a distinct change in terms of activity (in some subtypes of cells increased and decreased in others, as well as its natural self-destruction capacity) but not in the number of cells in people with CFS vs healthy people.

B cells have a phenotype (a form) that is due to cells exposed to viral infections or autoimmune disorders.

Furthermore T cells have a phenotype of anergic type (which are capable of eliciting a specific immune response) that could be related to the inability to control a viral infection that would result in the lack of activity and senescence (premature aging) showing the CFS patients.

The NK activity does not appear to be seriously impaired.

The results show GLOBAL immune dysfunction of unknown etiology (cause unknown) that could be the cause of Chronic Fatigue Syndrome.

Our preliminary considerations:

1.-Without going into too much detail, there are no serious anomalies at the level of cell numbers but in terms of how they work. Ie B cells, T and NK's are adequate in number but perform poorly.

2.-It is clear that if B and T lymphocytes are "parasites" by the XMRV will hardly be able to control viral infections occur opportunistically in people with CFS (EBV, CMV, HHV-6 etc) and Nor will be able to fight the growth of cancer cells.

3.-For the umpteenth time shows that the pattern of SFC's immune is strongly weakened (immunosuppressed) making it the focus of external attacks and causes your symptoms characteristic of the pathology.

THIS IS ONLY THE BEGINNING: THANKS A TOD@S!

Can Ruti These tests are only first steps on the XMRV work in CFS. Although everyone involved (patients and family members) are eager to do more studies, we know that these first steps are the most crucial if future studies then will be effective. So we want to thank everyone that when contacted from SFC League in late 2009 asking for donations and support for these trials, they responded positively with generosity and solidarity. Even those who worked to organize and participate in the concert in support of research XMRV Can Ruti-SFC in May this year in Barcelona. Your support was the seed of something very important. Thanks!

And thanks to the team of Can Ruti, Drs Cabrera, White, Clotet and others for their commitment to scientific research on CFS.

Thursday, September 23, 2010

Lidia Monterde. SFC League (Platform for Action)

Source: http://ligasfc.org/index.php?name=News&file=article&sid=364

It adds a little bit more background and some comments on those studies that we've already seen the abstracts of.

 

[Alexia]

It's really a very interesting report. I can understand Spanish well but the scientific terms make it difficult to follow everything.
It's great to see that they are busy trying to understand how XMRV "attacks " the body and what exactly does to the system once there.

 

[eric_s]

Yes. I think once they know where to look for the virus, other than in the blood, it should be easier to detect. And it's interesting to see how EBV etc. fit into the picture. Also good to have XMRV presence confirmed in one more european country. And they plan to do a larger study, it says.

 

[George]

This was great. It helped me to understand the EBV study more clearly. If I'm reading it right then they used cultured EBV cells to grow XMRV, kinda like they used the LnCap cells from prostate cancer to culture at WPI. That would mean that EBV activates XMRV right? That EBV actually gives the virus a place to make happy little XMRV children who then go out and make more happy little XMRV children.

So this would explain why the sudden onset. Most folks are exposed to EBV as children but may not develop "mono" until later in life or not at all. But if you have EBV then you have a place to replicate the virus, a good replication environment. Then later if you pick up EBV again in the form of mono or if you pick up a bug that activates mono then the XMRV explodes and it can take years for the body to rid itself of the XMRV but also to get the EBV under control again.

That is soooo cool. Science makes me happy.

 

[Enid]

Many thanks for this article. It is good to see Science (dedicated Researchers) unravelling the behaviour and interactions of these complex Virals.Another step along the way. And hopefully for us.

 

[eric_s]

I don't really understand it. Maybe someone with more knowledge can explain. What i understand is that they looked for XMRV in B cells that were transformed by EBV. And they found it there, so they say that these cells might be a reservoir for XMRV. I don't see any evidence that they tried to culture XMRV in this experiment.

But i find it interesting that there's some evidence that EBV might play a role. Because i've had it and it might well have been shortly before CFS started, because i had a rather bad infection then (but i can't know because i didn't take the test at this time only later and they could not say when the EBV infection occured). And EBV has always been discussed as a possible cause of CFS and now it feels a bit like the pieces are starting to fit together.

 

[julius]

This is a bit off-topic, and probably not of interest to many people here....but I thought I'd post it anyways.

This discussion on B-cells just gave me a huge eureka moment.

I have long known that cannabis offers me significant relief from my symptoms. It's not the 'high' that does it (I actually hate the feeling of being high...too anxious). It's aftwerard, when the high has worn off that I feel the relief. Mosly I feel reduction in inflammation, and much less brain fog, plus a lot less fatigue to boot.

I read a few studies of immune suppression by cannabis, and that made some sense to me (one of the main things I get from it is a major reduction in inflammation). But I never could fully understand how it applied to cfs. Now I think I have an idea how that might be working.

Cannabinoids bind with G protein-coupled receptors (these are the same receptors for androgens, and XMRV). Specifically they bind with CB1 and CB2 receptors.

Now, check this out...
"CB2 receptors are most commonly prevalent on B-cells, natural killer cells, and monocytes, but can also be found on polymorphonuclear neutrophil cells, T8 cells, and T4 cells. In the tonsils the CB2 receptors appear to be restricted to B-lymphocyte-enriched areas." (wikipedia)

So, it seems possible to me that the cannabinoids are blocking entry to the B-cells (and possibly other potential reservoirs).

Does this make any sense to any of you smarties out there?


ETA; I just realised that there is a hole in my thinking. XMRV binds with XPR1 receptors, so the cannabinoids blocking CB2 wouldn't be stopping xmrv entering the cell. But would there be another way that the CB2 receptors could be involved?