What does a neg XMRV really mean?

Discussion in 'Fibromyalgia Main Forum' started by karynwolfe, Jan 31, 2010.

  1. karynwolfe

    karynwolfe New Member

    Well, my disclaimer is that I'm not sure if this has been discussed before (i honestly stay clear of a lot of the XMRV posts here) but...

    I was just watching the Dr. Bell presentation link that both QuayMan and Gapscych have posted for us, and decided to make an admittedly premature post based on something that just struck me as interesting:

    Only 68 of 101 people in Mikovits et al. original paper on XMRV were positive for the virus using PCR...the same test a lot of us are paying large amounts of money to have done.

    But of the 33 people who were NEGATIVE for PCR tests...the virus was still there!

    In 10 of the negative-PCR group, the XMRV was actually there AND actively replicating; in 19 of the negative PCR group, there were antibodies that showed obvious exposure to XMRV; and in 30 of of those previously-negative 33, the virus was not only present but able to be transmitted!

    Now ideally a negative PCR means it's not in your blood, and a culture tests to see if it's in your cells (but not your bloodstream). But even in those people who were supposedly negative for XMRV in the blood, it was still found using the more expensive testing (which we normal-folk don't have access to yet...right?)!

    Dr. Bell said in this presenation that they ***do not yet know why this is happening***. They do not know why a virus that is obviously THERE and active, is not showing up in the PCR testing. (Sounds like Lyme disease, and the coinfections, which actually cover their own trail: If bacteria can do it, I don't see why a virus can't!)

    So truly, I think this is as good a reason as any to SAVE YOUR MONEY and not get the current XMRV test until they really know how to give you a definitive answer. Either a "yes you have it" or "no you don't." We don't want a "your test came back negative but that doesn't mean anything," like we have now... Just my opinion!

    [and please fill me in if I got anything backwards here, =) ]
  2. denis321

    denis321 New Member

    The culture test IS the test which is used to show transmission - i.e. the one where 30/33 people tested positive for although their PCR was negative. (The 10/33 refers to protein expression and not replication, different biological processes. This goes back to basic biology which I'm too tired to explain.)

    In a culture test, they take your cells/ plasma and place it next to cells without XMRV (not from you but obtained from a commercial lab). They then test the uninfected cells for XMRV after some time to allow exposure. If the previously uninfected cells now have XMRV, this is evidence towards your cells having an active infection and transmitting the XMRV. It's more complicated than this technically but this is the gist.

    The culture test is more time/ effort consuming than PCR but is a better test generally for other viruses/ bacteria and as these results seem to support, is also a more sensitive test for XMRV (until someone develops a better PCR test).

    NOW, these tests do NOT prove causality. When Dr. Bell was mentioning tissue culture that is something slightly different, more expensive, and might prove causality.

    I'm waiting a bit more for the validation studies to come in.

  3. ladybugmandy

    ladybugmandy Member

    i thought that 67% were positive by culture OR PCR and the others showed evidence of exposure via serology (antibody testing)?

  4. karynwolfe

    karynwolfe New Member

    My thoughts exactly; i keep hearing the tests aren't very reliable, and if they're not very sensitive, you could end up thinking you don't have this virus and yet you do...doesn't seem psychologically productive. =\

    We know it doesn't prove a cause, just that, it's there. Dr. Bell said, "And then 10 of the 33 had protein expression. What that means is when you look in the cells, you can find that not only is the virus there, it is making copies of itself, it is actually replicating, it is doing things." So when I said it was replicating, that is why.

    Are you sure this culture mentioned in the research is the same thing as what people are paying for? If it is, then why are people saying this test is not reliable enough to pick it up, if it's the same one used in the study? If the test is the same thing used in research, and the research picked it up in 99 out of 101...I can't understand that one.

    I typed that up there directly after listening to the presentation from Dr. Bell, so the 68 people originally found positive were only by PCR. The others were negative by PCR, but were found through other methods, and yes, testing for antibodies was one of those "other" methods... He listed in a slide that:
    -->DNA by PCR
    -->Viral infectivity
    -->Detection of viral proteins
    -->Antibody to the XMRV envelope
    were all ways to find the virus, but we do not yet have one gold standard that can be assumed to provide truly accurate results.
  5. denis321

    denis321 New Member

    If you are not aware, VIPdx changed their testing methods offered recently from:

    1. PCR *OR* Culture and PCR


    2. Culture only

    My understanding is that the culture test is the same as the one in the Science paper.

    1. When people report a negative, some only had the PCR done whereas others had both done.

    2. On the Phoenix Forums, the polls show that although some people were negative on both measures, there were more positives arising from the culture test than the PCR test. This is consistent with the small NCI data from CFSAC. So, it is not surprising to me that WPI is only offering culture now.

    The 99/101 number comes from people who have a positive on ANY of the four tests. So it's still possible to be negative on both PCR and culture test offered and be positive on protein testing (Western blot) or antibody testing later.

    The best thing might be for people to get all 4 tests done - 3/4 are ready to be licensed from the Mikovits talk, the next one being serology. The Western seems to be the least developed right now. Either all 4 OR a more sensitive one of those tests would be good.

    * Ladybugmandy, 67% refers ONLY to PCR. The Science paper actually does not mention how many positive Western blots, antibodies, or cultures were found in the controls. Only a few controls were used for these tests. Although Dr. M might have mentioned more during her talk - I have to watch it a couple times to absorb it all in and haven't done so yet.

    *Every individual has to make up their own mind when to get the test. There was a lot of talk about it on the boards and several well-known CFS docs did talk about waiting for a better test. [This Message was Edited on 02/01/2010]
  6. quanked

    quanked Member

    why do you steer clear of XMRV posts on prohealth?

    I came to the same conclusion about having the test(s) done. If I cannot get accurate results I wondered why bother. Too much emotional processing over something that is not definitive (not matter what the results might be) sounded like it would take more time and energy than it would be worth and really quite unncessary.

    I am just going to wait it out--if I live that long : )
  7. karynwolfe

    karynwolfe New Member

    I stay clear unless it's an article, I should correct myself. lol
  8. sunnyslumber

    sunnyslumber New Member

    I think the WPI retests sample periodically with different procedures. At least that is the impression I got from the Mikovits Presentation.