Spanish XMRV researchers to report Dec 9 on immune dysfunction

urbantravels

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A few bad word choices in the translation - I'm pretty sure that where it says "The possibility that pollution is responsible for sporadic detection of XMRV in humans." they mean "contamination", not "pollution." In other words the usual bullet point about Well, we don't know yet what these findings mean and it could be contamination.
 

floydguy

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A few bad word choices in the translation - I'm pretty sure that where it says "The possibility that pollution is responsible for sporadic detection of XMRV in humans." they mean "contamination", not "pollution." In other words the usual bullet point about Well, we don't know yet what these findings mean and it could be contamination.
Disappointing. I hope there is more to it than this.
 

Cort

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It almost slipped by me but I think this is actually very good news.....

3.- XMRV sequences can be found in patients with CFS but also in healthy donors or HIV+ patients. The copy numbers appear to be very low, and their pathogenic potential is unknown.

This means they found XMRV! What we don't know is what the percent positive are in the various groups. Low copy numbers are what we expect.....that's no problem. It appears they have a positive result :) - they just kind of covered it up.....
 

Hope123

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It almost slipped by me but I think this is actually very good news.....

This means they found XMRV! What we don't know is what the percent positive are in the various groups. Low copy numbers are what we expect.....that's no problem. It appears they have a positive result :) - they just kind of covered it up.....
It will also be interesting to know what %'s of healthy/ HIV+ they are seeing. The latter group is interesting because all the studies talked about to date that have involved HIV patients have not found XMRV.

Their first point talking about no "quantitative" differences also contradicts the initial thoughts on this thread re: low CD8 numbers. It appears the main abnormalities at least are not in low CD8 or other cell counts.
 

bullybeef

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I've just found the following posted on the SFC La Liga forum in September - it's news to me: http://www.ligasfc.org/index.php?name=News&file=article&sid=364

PRELIMINARY RESULTS OF TESTS CAN XMRV RUTI
Sent by edu - 1728 reads

Earlier this month in Washington DC, held the first international meeting of researchers on XMRV retrovirus, which is involved in the Chronic Fatigue Syndrome 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 presented studies that had also found this relationship, studies by Dr Paul Cheney, Dr. Kenny De Meirleir, 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 found 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 working 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 what the first two steps to detect this retrovirus. And thanks to these three trials, one can say it has succeeded in establishing the first steps to detect this retrovirus that presents a great difficulty in their detection.

Combining the 3 methods 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 the studies published in the U.S. although the team Can Ruti percentages do not enter it probably not statistically significant in a small sample. So it plans to expand the study with a larger sample in the near future as communicated in the press.

In any case the most relevant of these 3 trials could 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 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, 4 patients with HIV and 1 in prostate cancer tissue was obtained by PCR amplified genes ENV, GAG and POL (being the 3 genes that make up the XMRV) the following results:

ENV: 4 positive on 21 of which 3 with SFC, 1 healthy

GAG: 3 positive on 21 of them, 1 SFC, 1 healthy, 1 HIV

POL: 7 positive, 14 of which 4 SFC, 2 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 it confirms 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 in B cells that act as "reservoir" (the place where most viruses accumulate) of the 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, would dovetail perfectly 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 one of the possible reservoirs of the disease would find difficult to find copies of the blood and support XMRV trials with Rituximab and the like that cause a transient improvement of the disease by causing the destruction of certain B lymphocytes (CD19).

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

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

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

For this is done growing XMRV tonsil tissue causing infection at 7 days and superinfection at 14 days.

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 result in a reaction inmumolgica or kill them.

Our preliminary considerations:

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

2.-The study highlights that there is no difference in the 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, not kill 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 objective is to characterize 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 the activity (in a cell subtypes 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 incapable of generating a specific immune response) that may 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 cell numbers but in terms of how they work. Ie B lymphocytes, T and NK's are suitable 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 opportunistically that appear in people with CFS (EBV, CMV, HHV-6 etc) and will not be able to fight the growth of cancer cells.

3.-For the umpteenth time shows that the patient's immune pattern SFC is strongly weakened (immunosuppressed) making it the focus of external attacks and would suffer the symptoms of the disease.

THIS IS ONLY THE BEGINNING: Thanks everybody!

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 Can Ruti, Drs Cabrera, White, Clotet and others for their commitment to scientific research on CFS.
 

busybee

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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 what the first two steps to detect this retrovirus. And thanks to these three trials, one can say it has succeeded in establishing the first steps to detect this retrovirus that presents a great difficulty in their detection.
At last, someone who is more concerned about finding it than spending money on big numbers.

Thank you for this bullybeef.
 

eric_s

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Sasha

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Can somebody please post the content, for the people who don't have a facebook account?
Thanks
Here it is, posted on Facebook by Xand Xmrv:

My friend Cristina Montan has sent me this summary of what has been told in Barcelona this afternoon:

This Thursday, December 9, we had an event in Barcelona, in which the Spanish XMRV researchers explained their findings on XMRV in the Spanish CFS/ME population. This is a summary of what they said:

XMRV and CFS. WHAT SHOULD WE DO??

Controversy (scientific and social) has accompanied the retrovirus XMRV since it was identified in patients with chronic fatigue syndrome (CFS), a year ago. The disparity of results obtained by different laboratories and the scarce knowledge of this virus replication mechanism, have greatly limited scientific advances and therefore, their direct applicability to people affected. We need to reflect on the current situation so as to be able to define the steps that have to be taken by the various groups involved in the research of XMRV , whether they are health authorities, medical and research professionals, and of course, the people affected by CFS.

In the current situation, we should highlight these points:

1.- The lack of reliable detection methods for XMRV, that can be reproduced among different labs.
2.- The possibility that pollution could be responsible for sporadic detection of XMRV in humans.
3.- The findings of new MLV-related virus in patients with CFS (polytrophic viruses).
4.- Indentify XMRV sensibility to different antiretrovirals.

Considering the evaluation of our data set in the context of the knowledge we have of other retrovirus, we can point out:

1.- Patients with CFS have no quantitative abnormalities of their lymphocytes, though they show alterations in B cells (antibody producers), and in the NK and T cells (responsible for the destruction of infected cells). The functional implications of these alterations remain to be defined.

2.- XMRV can infect human cells in vitro, but we do not know its viral persistence mechanism (for new infections or survival of infected cells). These data are vital to determine the potential efficiency of antiretroviral treatments.

3.- XMRV sequences can be found in patients with CFS but also in healthy donors or HIV+ patients. The copy numbers appear to be very low, and their pathogenic potential is unknown.

At this time we are facing a potential health problem of unknown magnitude. It is therefore necessary to provide different scenarios for the future (both positive and negative) and to maintain preventive measures, while waiting for contrasted results by different labs giving us information about the extent of infection by XMRV and its role in CFS and other pathologies.

Dr. Juli Blanco
Irsi Caixa Foundation
 

alex3619

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From Post 27:

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

For this is done growing XMRV tonsil tissue causing infection at 7 days and superinfection at 14 days.

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 result in a reaction inmumolgica or kill them.

Our preliminary considerations:

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

2.-The study highlights that there is no difference in the 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, not kill 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.

Alex: this is important for two reasons. First it shows the results found in animals can be replicated in humans - nobody can argue that these results are just from animals. Second it gives us an additional reason for the low copy number of XMRV in blood: it is bound up in cells much more than expected from HIV and so researchers might not be expecting it. This might be why MLV researchers seem to be doing better than HIV researchers when it comes to XMRV. It also means that purified blood products like plasma would be much less infectious than whole blood if XMRV were present in the original blood product. I am less sure about blood platelets, but any blood product that has its white blood cells removed would be much safer.

Bye,
Alex
 

aruschima

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This is unbelievable great news!
This is the first serious research on XMRV and related viruses in Europe! And will have an impact on how other countries in Europe, even the states will tackle the issue of finding XMRV !

(George, I am surprised your not having another "all pieing over the carpet" moment :D ?!

VIVA SPAIN! (This cfs lega has 4000 members !)

3.-There seems to be enough evidence to believe that the XMRV infects lymphocytes, but unlike HIV, not kill 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.
I wish we would have an exact translation of the transcripts !

Just a small additional information I stumbled over while looking up info on B-lymphocytes ( might be relevant to this topic)
Epstein–Barr virus (EBV) is a human herpesvirus with tropism for B lymphocytes, although it can also infect epithelial cells. In a healthyindividual, EBVestablishes and maintains latencyin a relativelysmall number of memoryB cells, remaining quiescent. However, viral inactivity is stronglydependent upon the continuous activityof cytolytic CD8+T lymphocytes (CTLs), and infected hosts also have serum antibodies to proteins expressed in the viral lytic cycle (reviewed in [1]). Thus, conditions resulting in immu- nosuppression allow EBV to promote unregulated B-lymphocyte proliferation and/or survival. B-cell tumors directly associated with EBV-mediated transformation arise in pharmacologically immunosuppressed patients (such as transplant recipients), HIV-infected patients, and persons with the genetic disorder X-linked lymphoproliferative disease (XLP).
 

aruschima

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Yes, Eric, this was from September. However, this fairly new and is the next step :

In the same event, we, the Liga SFC (http://www.ligasfc.org), will launch a new association of health professionals in support of ME (ASSSEM - will be at http://www.asssem.org, under construction) which will present a document we have written for patients to take to their family doctors and other doctors.

ASSSEM's strategy is to bypass the CFS units the goverment has set up (which are "fibro-parkings": they only park you with useless medication and cognitive behavior therapy) and go directly to the experts:
• Immunologists (not many in Spain),
• Infectious disease specialists,
• Virologists,
• HIV doctors, etc.

Here is the announcement of the Dec.9 event in Spanish: http://www.ligasfc.org/index.php?name=News&file=article&sid=376 [click the “Translate” button for a rough English version].

The document we have put together goes beyond the Canadian Criteria because the findings of the past year or so go WAY beyond Carruthers et al. We hope bad health will not interfere too much with our translating the document to English in the next month or so.
Exiting for me, as European, cause until now, I did not see any independent research or any efforts made at all. This , I think , is independent research efforts and goes a step further ? Going beyond the Canadian Criteria ! A strategy is to bypass the CFS units the goverment has set upThis is exactly what I was hoping for. Bypassing governments and validating the disease with a new Criteria, validating immune abnormalities is exactly what we need, the next step I was hoping for !

Honestly, this is the first real action I have seen and shows the confidence the other efforts all have lacked . Great stuff !
 
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Cort, Irsi Caixa already reported XMRV+ sequences last September in the XMRV workshop

Basically, yesterday they did not say anything new as it was expected in terms of the immune system of CFS patients...but we were not looking for a XMRV+ study, because that was already known since September.

They could have talked about the particularities found in the immune system of CFS patients, and maybe they did, but in the summary there is not much detail on it. Lets wait until the conference is posted in the web of clara Valverde to see if there are some more details...

Grettings

C.
 

aruschima

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And by the way, a great example for you guys in the states, who still argue about the name changes/CAA/or the shameful display of utter incompetence by the CFSAC.

Sorry, but I could not restrain myself :D

I am joining the Catalan's :victory:
 

George

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(big grins) Actually I peed the carpet last September. But yeah it makes sense that this is mostly bound up in B cells and that's probably why it becomes activated during a heavy viral illness like Mono, or Q fever or take your pick. I'm thinking the primary reservoir is going to be bone marrow much like FLV in cats. I was hoping for a little more of a prodding from Spain but I'm very happy that Spain and Norway seem to be forging ahead despite the delay's here in the US. Where due to lack of information from our government we have nothing better to do than debate the role of the CFSAC. (sigh)