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It's the Antibodies Stupid, (big grins)

Discussion in 'XMRV Research and Replication Studies' started by George, Oct 29, 2010.

  1. George

    George waitin' fer rabbits

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    Characterization of antibodies elicited by XMRV infection and development of immunoassays useful for epidemiologic studies

    Xiaoxing Qiu1 email, Priscilla Swanson1 email, Ka-Cheung Luk1 email, Bailin Tu1 email, Francois Villinger2 email, Jaydip Das Gupta3 email, Robert H Silverman3 email, Eric A Klein4 email, Sushil Devare1 email, Gerald Schochetman1 email and John Hackett Jr1 email

    1 Infectious Diseases R&D, Abbott Diagnostics, 100 Abbott Park Rd, Abbott Park, IL, 60064, USA

    2 Department of Pathology, Emory University School of Medicine/Yerkes National Primate Research Center, 954 Gatewood Dr, Atlanta, GA, 30329, USA

    3 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Av, Cleveland, OH, 44195, USA

    4 Glickman Urological and Kidney Institute and LRI, Cleveland Clinic Foundation, 9500 Euclid Av, Cleveland, OH, 44195, USA

    author email corresponding author email

    Retrovirology 2010, 7:68doi:10.1186/1742-4690-7-68

    The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/7/1/68
    Received: 3 June 2010
    Accepted: 17 August 2010
    Published: 17 August 2010

    2010 Qiu et al; licensee BioMed Central Ltd.
    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Abstract
    Background

    Xenotropic Murine Leukemia Virus-related Virus (XMRV) is a human gammaretrovirus recently identified in prostate cancer tissue and in lymphocytes of patients with chronic fatigue syndrome. To establish the etiologic role of XMRV infection in human disease requires large scale epidemiologic studies. Development of assays to detect XMRV-specific antibodies would greatly facilitate such studies. However, the nature and kinetics of the antibody response to XMRV infection have yet to be determined.
    Results

    Three rhesus macaques were infected with XMRV to determine the dynamics of the antibody responses elicited by infection with XMRV. All macaques developed antibodies to XMRV during the second week of infection, and the predominant responses were to the envelope protein gp70, transmembrane protein p15E, and capsid protein p30. In general, antibody responses to gp70 and p15E appeared early with higher titers than to p30, especially in the early period of seroconversion. Antibodies to gp70, p15E and p30 persisted to 158 days and were substantially boosted by re-infection, thus, were identified as useful serologic markers. Three high-throughput prototype assays were developed using recombinant proteins to detect antibodies to these viral proteins. Both gp70 and p15E prototype assays demonstrated 100% sensitivity by detecting all Western blot (WB) positive serial bleeds from the XMRV-infected macaques and good specificity (99.5-99.9%) with blood donors. Seroconversion sensitivity and specificity of the p30 prototype assay were 92% and 99.4% respectively.
    Conclusions

    This study provides the first demonstration of seroconversion patterns elicited by XMRV infection. The nature and kinetics of antibody responses to XMRV in primates were fully characterized. Moreover, key serologic markers useful for detection of XMRV infection were identified. Three prototype immunoassays were developed to detect XMRV-specific antibodies. These assays demonstrated good sensitivity and specificity; thus, they will facilitate large scale epidemiologic studies of XMRV infection in humans.
     
  2. George

    George waitin' fer rabbits

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    I know this is old but that's kinda my point plus, I couldn't remember seeing it before. Anyway how can there be any question, anywhere about contamination when we have indisputable antibodies?????
     
  3. Jemal

    Jemal Senior Member

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    Beats me... my feeling is that there's too much politics going on.
     
  4. floydguy

    floydguy Senior Member

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    After meeting Dr. Mikovits and listening to her speak in NJ, there is little doubt in my mind that the contamination issue is BS at this point. For whatever reason people seem to be spreading fear, uncertainty and doubt. At the very least we should be carefully documenting who is doing this and try to figure out why they are doing it.
     
  5. natasa778

    natasa778 Senior Member

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    Than you really shouldn't be on this forum, where people say things :D Just stick to pubmed from now on.


    I'm with floyd ;)
     
  6. alex3619

    alex3619 Senior Member

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    Hi

    Just a general comment on documenting details of what is happening: to me this is about getting evidence to determine what is happening. Its about understanding not witch hunts. The published science can be years behind the cutting edge, and we want to understand where the cutting edge is right now if we can. Millions of lives and livelihoods are at stake, so we want information. We aren't going to get certainty in our lifetimes, no matter the science, so its about reading the events - including good published studies - so we can plan our futures.

    Bye
    Alex
     
  7. ukxmrv

    ukxmrv Senior Member

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    It's the lack of technical explanations that is causing people to discuss the politics, KFG. Some of us have been emailing and talking to as many researchers as we can to try and determine this. However the people who insinuate contamination are largely not providing proof or even theories.

    That's what we want to see, real concrete proof. Not so a particular theory can "win" or lose but because we want to know the truth.

    Dr Huber for example reported on possible contamination of her own heparin tubes from China. Apart from Dr Huber the others appear not to be able to explain a mechanism for the contamination or answer the question about antibodies.

    Robin Weiss mentioned possible contamination from Taq polermaise may possibily ontain X-MLV's

    We have been trying by whatever means are available to us to get the answers so we patients will have the data and can make reasonable assumptions.
     
  8. George

    George waitin' fer rabbits

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    Wow, touchy subject KFG??(grins) Thanks for the nod I promise to check my wording twice. (big grins)

    As for the point I was getting at, we now have Cleveland clinic, NCI, WPI, NIH, FDA, ARUP, Abbot Diagnostics and many others, (It's kind of a long list on the prostate cancer side), who can find both the virus and antibodies. That flies in the face of Dr. LiGrice's statements at the CFSAC. I'm still very miffed about Dr. LeGrice and that other guy because the statements were out and out lies with documentation plan as day to show they were lies. I don't know anybody who likes being lied to. There is something about it that just makes you want to bite someone. (o.k. maybe the biting thing is just me)

    So the point is pretty much what floydguy said, who and why? (grins)

    First, why so that we know as a patient community what we have to deal with, both in terms of letter writing campaigns, media or other but also the tone of those campaigns. Does it need to be stronger or softer or fall in the category of kicking ass. For instance anything concerning the CDC needs to be in the kicking ass grouping (big grins) cause if not the only thing left is the "beating a dead horse" category.

    Second, the who is a bit more problematic because unless you understand the "why" its hard to know if the "who's" are sacrificial lambs or goats in some cases and if targeting them is a waste of time or if pressure needs to be applied to them as well as their bosses or if the person is just smoke and mirrors. Face it we all have limited resources both energy and financial so it has to applied carefully. But pressure needs to be applied because as most of us have learned in this world the really squeaky wheel gets the grease.

    So it's up to us to figure out how to pull the curtain back and show the little guy pulling the levers. Only by keeping the pressure at the proper point will we end up with some or most of what we need.

    This community really doesn't ask for much on the whole. Mostly we want to be acknowledged as a group with a biological illness . That's not asking for much. Most of us don't even care if it's XMRV or not, just getting past the pscyobabble is a major goal. We would like adequate funding for basic clinical trials. We have never had trials for basic treatments like what kind of exercise or not to exercise at all, sleep help, understanding of our vitamin and mineral imbalances, help with OI or problems with leaky gut, the simple things. Most of us would be fine with 40 or 50 million a year just to get us to that point.

    The fact that we are this far behind the curve means is kinda crazy. Then to be presented with such a pretty package called XMRV all tied up with a lovely ribbon of serious retrovirus on it is just too good of an opportunity not to use to our advantage. It doesn't matter if XMRV turns out to be part of the problem, most of the problem or all of the problem (NOTE:if we are producing antibodies then it is most defiantly a problem!). You don't produce antibodies to things that are not a problem for your body, so it's up to us to push as hard as we can now in whatever ways we can or choose to.

    If we keep feeding the information back into the community and the media, keep the pressure on we can end up in a really good place when the dust settles.

    Wow, that was a ramble! Thanks in advance for bothering to read all that. (big grins) Anyways anyone want to make sure Amy Docker-Marcus has a copy of this would be great. Anybody want to make up a little timeline of who said what to whom and the science or transcripts that give lie to those statements and send them to Amy or others would also be great. It's important that we apply enough pressure to be a threat. If we don't let em get away with BS and show em just how smart we really are it will help to keep em honest. (big grins)
     
  9. Sean

    Sean Senior Member

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    Er, that already happened to us patients a long time ago. More than a few in power don't think we are really even entitled to a view at all, and should just shut up and take our damn 'medicine'.
     
  10. Fejal

    Fejal

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    Because it's only in 67% of the patients. What is infecting the other 33% who don't have XMRV? What about the french study that found that most of the patients had a completely different virus MLV? Therefore XMRV antibodies aren't the problem.

    Koch's postulates are:

    1.The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy animals.

    6% of patients with XMRV are healthy.

    2.The microorganism must be isolated from a diseased organism and grown in pure culture.


    3.The cultured microorganism should cause disease when introduced into a healthy organism.


    Did the monkey's get CFS? No.

    4.The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

    http://en.wikipedia.org/wiki/Koch's_Postulates
     
  11. lansbergen

    lansbergen Senior Member

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    Are these animals not housed in a germfree environment?

    Patients are told there is nothing wrong so why would these researschers be able to see it in animals?
     
  12. leela

    leela Slow But Hopeful

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    I wonder if you might consider taking your own advice in this department.
    Maybe I'm missing something, but to me your response seemed wholly out of proportion to the previous poster's intent/content.
     
  13. Stone

    Stone Senior Member

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    One thing that I would love to hear explained about the contamination theory is how in the sam hill you can get a much higher rate of contamination in people with our disease compared with healthy controls. If contamination were an issue, then wouldn't one expect to see the number of "false" positives be about the same in the disease group as the control group?
     
  14. eric_s

    eric_s Senior Member

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    It might have to do with samples of cases and control being handled differently. But if a study is really totally blinded and samples are collected in the same way this should be ruled out, i guess. So far most positive studies had some differences between how samples of cases and controls were collected and/or stored or were not blinded, as far as i know.
    That's what i've been thinking since spring. Just send 50 or so samples to VIP Dx, half of them cases, half of them controls, freshly collected in the same way, without VIP Dx knowing. If you get a significant difference in positives... Bingo, no more questions about if there really is something there. I actually wanted to go about trying to do this, but then the Alter study came out and the XMRV workshop was coming up, so i thought it's not necessary anymore.
     
  15. lansbergen

    lansbergen Senior Member

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    IMHO it should be about the same percentage.
     
  16. George

    George waitin' fer rabbits

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    Hey KFG
    I so hear ya, that was so me a couple of weeks ago. It just seems sometimes like the world is "through a glass darkly" some days. The great thing about the bad days is that they usually lighten up so it's something to look forward too. (big grins) Course when I'm going through it I have to hang out the "Beware of Dog" sign. (sigh)

    Hey Fejal, I think we are all pretty much aware of your take on things. I never try to convince those who are locked in on a particular course. It's like trying to change the trajectory of a rocket once it's been launched. (grins)

    I would point out for anyone else interested however that Koch actually revised his own postulate's which were first formulated in 1890

    There will always be "carriers" it turns out. As for the monkeys becoming ill we don't understand this particular illness or virus well enough at this point to say definitively but some things to consider might be as follows;

    1- in mice MLV normally begin to show symptoms in "laboratory infection" in about 21 days however that's in mouse time. Kinda like dog time ya know? In human time 21 days could be months or years.

    2-it's been speculated that a triggering event of some sort must first occur if the monkey were not "triggered" then no illness would be expected to be evident. In addition, these monkey were sacrificed in less than a 6 month time frame so there wasn't much of an chance to observe if the monkeys might have developed any symptoms before they were killed.

    3- At this point no one is saying that XMRV is the cause of ME/CFS (see above long post, grins) the discussion at least from down here at a dogs level is just about the antibody response and the fact that it flies in the face of the established ideology that MLV type viruses can infect primates at all and even more importantly cause an antibody response as a foreign invader.
     
  17. FancyMyBlood

    FancyMyBlood Senior Member

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    Fejal, I hope nobody here takes you serious anymore. You did a very nice job cherry-picking again!
    That wiki page also states that "Koch abandoned the universalist requirement of the first postulate altogether when he discovered asymptomatic carriers of cholera and the third postulate specifies "should", not "must", because as Koch himself proved in regard to both tuberculosis and cholera,[2] not all organisms exposed to an infectious agent will acquire the infection". You 'forgot' to mention those two facts.

    Many people have virusses/bacteria and never get sick. For example EBV. And it doesn't say anything that the monkeys didn't get CFS; 1. XMRV could only manifest CFS like symptoms in humans. 2. They had a proper functioning immune system 3. XMRV could get activated by other virusses (viral onset CFS) 4. It could take years to develop these symptoms. (HIV=>AIDS).

    I don't think your ignorant/stupid. It's even worse, you deliberately distort information to spew out your own Marshall propaganda. Where have we seen this before?!
     
  18. eric_s

    eric_s Senior Member

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    Maybe there was a misunderstanding. I also don't like the idea of making records about who says what on a forum, but if that poster was talking about monitoring what scientists and politicians do, i think the idea is not bad. One day, when things are more clear, i would like to try to make sense of this weird situation. See who was right and who wasn't and for what reason and if it can be justified or not.
     
  19. leela

    leela Slow But Hopeful

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    For what it's worth my take was that the original post was talking about monitoring the science/politics of ME/CFS and who is doing what to suppress or distort
    emergent info. But I too am having a horrible brainswell day, I feel dreadful, so I can't speak for anyone else I guess. That was just how I read it, and I get touchy when people jump on each other. 'Specially when I feel like my brain is being filled with molten something-unpleasant.

    As for the monkeys, they are eventually "sacrificed" and I do not remember anything about if or when they were indeed terminated. They may no have had time, or as others have said, sufficient triggers to contract what we call ME/CFS. Certain posters are invisible to me, by the way, so my posts here may be a little out of synch.
     
  20. natasa778

    natasa778 Senior Member

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    Kochs postulates in the 21st century

    http://www.virology.ws/2010/01/22/kochs-postulates-in-the-21st-century/


    ....Despite the importance of Koch’s postulates in the development of microbiology, they have severe limitations, which even Koch realized. For example, he believed that cholera and leprosy were caused by microbes, but could not fulfill all four postulates. Furthermore, Koch knew that the putative agent of cholera, Vibrio cholerae, could be isolated from both sick and healthy people, invalidating postulate #2.

    The limitations of Koch’s criteria are even more obvious when we consider viral diseases, which were not yet discovered when the postulates were formulated. Thomas Rivers, who has been called the ‘father of modern virology’, wrote:

    ‘‘It is unfortunate that so many workers blindly followed the rules, because Koch himself quickly realized that in certain instances all the conditions could not be met. . . . Thus, in regard to certain diseases, particularly those caused by viruses, the blind adherence to Koch’s postulates may act as a hindrance instead of an aid.’’

    Many viruses do not cause illness in all infected individuals, a requirement of postulate #1. An example is poliovirus, which causes paralytic disease in about 1% of those infected. Further compromising postulate #1 is the fact that infection with the same virus may lead to markedly different diseases, while different viruses may cause the same disease. Postulates #2 and #3 cannot be fulfilled for viruses that do not replicate in cell culture, or for which a suitable animal model has not been identified.....
     

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