Gulf War Veterans Study Recent Developments re Civilians with CFS/ME and XMRV Research: Why?

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Gulf War Veterans Study Recent Developments re Civilians with CFS/ME and XMRV Research:  Why?

Unanswered Questions Continue For Ill Gulf War Veterans As They Do For Civilians With CFS/ME

Many have asked me why am I tracking this development over the past year since the first paper on XMRV was published.  Will since the very beginning(1991-1992) I connected with the Civilian Chronic Fatigue/ME groups I learned from them a lot!  We have had several of them come to hearings on Gulf War Illness and one attended a Veteran’s Affairs Research Advisory Committee on Gulf War Illness.  Since then we have had some of the CFS/ME Researchers present their findings to this same advisory committee including Dr Kerr.  We now have Dr Klimas also working with Gulf War Illness, Dr Barinuk doing research with gulf war illness, and in the past Dr Berg(hypercoagulation).

I have been exploring the big picture!  I also know we had veterans who were nondeployed that got ill and have had little attention paid to them and their struggles to get help and any compensation.  I have always felt we had multiple exposures and that this was possibly a snowball that grows to an avalanche.  Each exposure is important and a synergistic effect has not been disproven! 

Also we had Gulf War Veterans who are ill also with family members (healthy before the war) that got ill with CFS symptoms and we had gulf war veterans reporting that their children born after the war had attention disorders/autism.  I found it interesting at the OFFER conference in Salt Lake City that there were at least 8 family members of Gulf War Veterans out of an estimated 300 patients at their patient conference .

Gulf War veterans were put into the mix with our law that connected Chronic Fatigue, Fibromyalgia, IBS, and menstrual cycle problems for our female veterans.  Many Gulf War Veterans have been going to civilian doctors that have civilian Chronic Fatigue patients to try and find real help.

None of us have the answers yet.  But I do feel we need to push and have studies with each subset and Gulf War Veterans being one subset to be tested.  We need to find out how we are different and how we are alike in each diagnostic test.  For example immune system problems, autoimmune problems, autonomic nervous system dysregulation, and differences and similarities in our test results.  Dr Klimas and Baraniuk are two of many that could help us get more answers.

WE do not know for sure which exposure is significant for each veteran.  We do not know if there is a genetic suspectibility to one exposure versus another or how the exposures act synergistically.  We do not know if exposures to the vaccines or contamination from returning equipment impacted the nondeployed veterans or civilians that worked at the ports receiving our equipment as it returned like we did in 1991 or civilians that worked with the DOD who got ill.  WE do not know if any of the civilian sufferers had exposures to vaccines we got or equipment that was returned from the gulf.  We do not know if the civilians ill in Salt Lake City has any correlation to testing that was done at Dugway proving grounds.  We do not know if civilians in Nevada or elsewhere where chemical exposures or radiation exposures could be part of the mix in their illnesses.  We do not know the susceptibility to infectiousness.

These are the questions that keep me questioning and pushing me to continue to explore all the research.  In that quest I share the information I am finding in the civilian Chronic Fatigue Networks and other networks to include MS groups, MCS groups, Cancer groups, Atomic  and other exposed veteran groups, and so many others.  I do know we all need to network and push for answers.

It is a bad mark on this country when ill gulf war veterans have to keep the pressure on to get help.  Be it pushing for hearings, pushing for release of classified documents, to attending research advisory committee meetings, and then also having to go beg US Representatives and Senators to fund meaningful research through the DOD CDMRP and getting a very small amount each year!  The veterans continue to fight the VA to do the hard research and fund really strong research and the efforts to find biomarkers and treatment for gulf war veterans.  The announcement of their last response ( VA funded Gulf War Illness Research) to our needs has met with criticism and a loss of hope that they get it at all!  WE need the best and the brightest!  WE need it NOW.  WE do not need half steps.  It has been 1991 for the gulf war veterans who are desperately ill and wanting real answers and real help.  WE live in every state and overseas.  Our coalition forces are ill too!  We should leave no stone unturned and neither should we leave people ill and sufferring.  That means we need to consider our nondeployed that are ill and learn from other groups.  Whether you have MS, ALS, thyroid problems, cancers, autoimmune problems we veterans need to remember to not splinter and not support the big picture!

The same is happenning to the Chronic fatigue patients in civilian life.  Statistics from their site:  •Asthma: $10 billion economic losses year
•Asthma funding:$300 million a year
•ME/CFS: $20 billion economic losses year
•ME/CFS funding: $4 million a year
•AIDS – $2700  per person 
•Asthma – $300 per person
•Chronic Fatigue Syndrome – $4 per person

Very Very Similar to Gulf War illness research fight for funds.  I do believe we need some cost figures always highlighted at least one in four of gulf war veterans from 1990-91 affected, that is a big number especially if we have coalition forces counted,  then should we add? ill non deployed, plus ill DOD or Civilians directly connected to Gulf War 1990-91 health issues.  And that number continues to grow!  How much loss per veteran if they had been healthy and able to work?  How much impact to their local economies much less at state level?  How do we compare to research done on AIDS and other illnesses?

So below is report on abstracts from the international meeting that occurred just this past month on XMRV thanks to the CFS/ME patients and advocates. 
I await Readers’ comments and hope that each person that is reading responds with some type of comment.

  • XMRV International Workshop Abstracts Part I 

    Those Monkeys – Five Rhesus macaques were infected with XMRV; two of them were sacrificed quickly and the others several months later. Creating only low levels of antibodies, the immune system did not react strongly to the virus possibly because it was able to quickly remove the virus from the bloodstream. This apparently suggested to the investigators that the virus showed low infectivity and virulence, but low and behold when they opened the animals up, they were surprised to find that the virus had infected many organs and they were able to detect evidence of ongoing replication. Interestingly, the virus hung out in the lymphoid organs – which give it a clear pathway to the bloodstream. (Dr. Mikovits has suggested that the lymphoid organs could be a tissue reservoir for the virus). They found that XMRV was also replicating in all the sexual glands – which, of course, suggests that sexual transmission is a distinct possibility.

    XMRV is Different in the Prostate  – we’ve heard that different XMRV variants may exist in the blood and the prostate but this study suggested that the XMRV may be different within the prostate itself. This study found different forms of XMRV which, the authors speculated, could enhance XMRV’s ability to cause prostate cancer (if indeed it does that).

    XMRV Is Not Present in Prostate Cancer in the US – While several positive prostate cancer XMRV studies have occurred this fairly large John Hopkins study, which used immunohistochemistry, found zero evidence of XMRV in almost 200 samples…But…

    XMRV IS Present in Prostate Cancer in the US – a Baylor study found XMRV was present in 22% of 144 prostate cancer patients – so much for consistency at this stage of the game. Still a positive report should trump a negative one, all things considered. Two more US studies will alternately not find and find XMRV in prostate cancer patients.

    Hanson XMRV CFS Study Strongly Positive – This is the first study to use LnCap Cells (aka WPI) to culture at least some of the blood samples. Reports from the conference suggested that Dr. Hanson found polytropic MLV’s but no XMRV but her abstract stated her study was strongly XMRV positive with XMRV gag sequences showing up in just over half the CFS patients. The abstract ends “Our results corroborate those of Lombardi et al (Science paper)”! Dr. Hanson is the first recipient of an NIH grant to study XMRV in CFS patients and her extensive study to examine the immune factors and the effects of exercise on XMRV is projected to take at least a year.

    Yes, There is XMRV in the UK – This UK study with Dr. Mikovits in the lead and Dr. Ruscetti the senior author, states that ‘more sensitive’ methods to detect XMRV have been developed since the Science paper was published last October. The blood was collected in England and shipped to the National Cancer Institute in the US. They came right out and said it’s not about the methods – that the most important factor in the negative results in the type of patient studied a theory which seems to have gained some strength lately. The paper states  “Since the most important variable in detecting XMRV in CFS is patient selection” – an interesting statement, if there ever was one.

    They used five methods, the most prominent of which was culturing in the LnCap cells that Dr. Hanson used but they also used antibody tests and various kinds of PCR tests on different types of cells. The WPI has been working hard on the diagnostic end as they cited their new antibody tests and new primers that can detect both XMRV and polytropic MLV env sequences. They also showed, as did the Science paper, that cell free media from patients contained the virus (it was present in the blood outside of the cells) and that the virus could infect other cells once they were placed in it; no wonder Dr. Ruscetti reportedly claimed his work on the diagnostic end was over and he was moving onto the next stage of research. This was a very strong study – with multiple overlapping tests – just as occurred in the original Science study.

    A New Method For Detecting XMRV
    –  Dr. Ruscetti has developed ‘DERSE’ cells that can quickly and sensitively detect the presence of XMRV – another diagnostic improvement in a Workshop that was chock full of them.

    ‘High Throughput’ Antibody Tests Available
    – want to test large quantities of blood for antibodies to XMRV? The authors think they can now do that.

    Blood Working Group Has Been ‘Working’ – Not very fast but they are working. They are now very clear that they have a good test to detect XMRV in spiked vs unspiked whole blood, PBMC’s and plasma. Next step is looking for XMRV in people!

 

  • XMRV International Workshop Abstracts Part II:

    German Researcher Draws Blanks Again – Norbert Bannert is not having an easy time with XMRV. First he tried to find it in prostate cancer and failed and now he’s to find it in ME/CFS and failed. Unlike other researchers he activated the PBMC’s he sampled and then cultured them in order to boost the viral presence but he used a different process than the WPI and Dr. Hansen did. Then he tried to transfer the virus to the LnCap cells the WPI does use in at least some samples but to no avail. He did show, though, that XMRV is infectious; that is he was able to produce the virus from a cell line and showed that it could infect cells. His particular population – a small group of 39 CFS patients – was negative, as were his healthy controls and a group of MS patients.
    Swedish Study Comes Up Empty – Dr. Blomberg and his ‘Swedish XMRV Study Group’ – used quantitative PCR – the same type of PCR Dr. Singh favors, to look for XMRV. Dr. Blomberg used the same LnCap cells the WPI recommends to culture the virus for five days for the same period of time the WPI recommends. Blomberg found no XMRV in 50 people with ME/CFS, 400 prostate cancer samples or 200 controls using what he called his ‘novel’ PCR methods. He did get a few weakly positive (or ‘uncertain’) samples from ME/CFS patients. We can see from both these studies and the Mikovits and Hansen studies that as time goes on studies are getting more complex and are starting to hue more towards using the WPI’s techniques. Dr. Singh is currently engaged in an XMRV study in Salt Lake City which is using LnCap cells as well.

    XMRV Blood Working Group is Halfway There – Key Problem Identified? Phase II of the project, which compared different labs ability to find XMRV in WPI identified positive patients is complete! One thing they looked was whether the 2-4 day delay in processing that is common in many labs affects a labs ability to find the virus. Dr. Mikovits’ stated that blood preparation techniques are important and it brings to mind Dr. Singh’s painstaking attention to this factor in her study. In Phase III they will determine the best assay using blinded tests and in phase IV they will look at 300 samples from the Western United States. They will be done by the end of the year.

    Finding XMRV’s Tissue Reservoir – Dr. Ruscetti stated that the results from the Science paper suggest that XMRV is not very active in T and B cells in the peripheral blood – the main players in the adaptive immune response. His study looked further into the immune system and found that it can infect two major players in the innate immune response – monocytes/macrophages and antigen presenting dendritic cells. Interestingly, while XMRV appears to be able to infect and replicate in these cells, MLV’s cannot – the reason being that they cannot infect ‘non-dividing cells’. Ruscetti is currently investigating whether XMRV is infecting a small number of macrophages/dendritic cells that are dividing.

    XMRV and the immune System – MLV’s have a history of producing cancer and neurological disorders in rodents and other mammals but what about those immunologically disturbed ME/CFS patients? Does XMRV do anything to disturb the immune system? This study, which looked at how the gene expression in prostate cells changes when they become infected with the virus, found a good deal of abnormal immune and other gene expression. The authors stated their findings suggest the virus could have a ‘profound effect’ on fundamental cellular physiology and inflammation.

    XMRV and EBV Team Up?a Spanish team found that XMRV in a significant percentage of EBV transformed (infected?) Cell Lines from a small group of ME/CFS patients and healthy controls suggested that EBV infected B cells could be a tissue reservoir for the virus.

    XMRV Present in Leukemia and Mantle Cell Lymphoma Cells
    – Dr. Mikovits and Dr. Ruscetti and others found XMRV in leukemia and Mantle Cell Lymphoma cells from two patients. The abstract suggested that the development of these cancers ‘coincides’ with three factors; the growth of the gamma delta T-cells, XMRV infection and a ‘distinct inflammatory profile’. They appear to suggest that these factors could place patients at risk for the development of these cancers. (Interestingly, neither EBV, nor HHV-6 or CMV appeared to coincide with cancer development). They also noted that antivirals can help in HIV derived cancers and that AZT and Raltegravir stopped and significantly reduced previously rising lymphocyte counts in one XMRV infected ME/CFS patient with cancer. This suggests antiretrovirals may be helpful in this set of  ME/CFS cancer patients.

    Dr. Cheney ‘s Study Dr. Cheney’s study probably did little to answer any of the more pressing questions about XMRV because the tests were not done at an independent lab but it should prove quite valuable when the WPI’s XMRV test is validated. Some of his stats were alarming. Dr. Cheney has said he probably sees a sicker population and judging from this sample he probably is; the average duration was almost 20 years! He found XMRV in almost 75% of them. His patients had a very high incidence of CFS or CFS-like illnesses in their family (45%); 48% had cancer in their families or themselves and 28% had autoimmune diseases in the family. (One wonders what the norms are.) The most startling fact was 50% XMRV positivity in non-CFS family members. If Dr. Cheney is right this virus is spreading in families.

    XMRV Positivity Rates at VIP Dx – In the 7 months between November and May VIP Dx Labs received 712 samples (about 100/month) from 46 of the 50 states in the US and about 50 from Europe and the UK. Of those only 35% tested positive for XMRV. The discrepancy between Dr. Cheney’s 75% and VIP Dx’s 35% is surely one reason why Dr. Mikovits stated the type of patient being tested is a major factor in the positive rates for a test. Of course, Dr. Cheney with his 20 year ME/CFS patients was undoubtedly testing a severe subset.

Children with XMRV – the Ruscetti/Mikovits juggernaut rolled on with their (fourth?) abstract, this time indicating that XMRV was present in no less that 82% of 17 autistic children (!) The finding that 16 of the 17 families with autism spectrum disorder, CFS, FM, Lupus, etc. had at least one member infected with XMRV suggested that it may run in these diseases, although.

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