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Given Dr Lerner and Montoyas findings, why arent a subset of us getting treated now?

Discussion in 'Latest ME/CFS Research' started by snowathlete, Nov 3, 2011.

  1. searcher

    searcher

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    Timaca- Thanks for that update. I was told a few weeks ago that some other research was taking priority, and I mistakenly assumed that meant the pathogen study was getting delayed. It's going to be great to get the results of those tests, and hopefully a lot of us can share what is found so we can try to extrapolate what the results means for the whole community.
  2. Hip

    Hip Senior Member

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    Nice find, searcher.

    I have just now included these titer refs in the CFS Testing & Treatment Roadmap

    Is this "4x theory" a sort of rule of thumb?

    The other thing is the EBV titer interpretation, I believe, can depend on other titer factors, like VCA-IgM, EA and EBNA, as Tristen mentions:


    Here are a couple of webpages on EBV result interpretations.

    Interpretation of Epstein-Barr Virus Serology

    CDC: Epstein-Barr Virus and Infectious Mononucleosis

    I will read them when I am more mentally sharp.


    Also, my own lab results for HHV-6 are this (typed out word for word):

    This last sentence in italics is another proviso that may need to be included in the roadmap guidelines.
  3. Hip

    Hip Senior Member

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    Also, does anyone know the correct way to convert between antibody testing results from titer figures like 1:160 to index values like 7.0, and also to IU/ml values (= international units / milliliter).


    I have assumed that the index value is some kind of logarithm of the titer value.

    So for example, would 1:160 have an index value of log(160) = 2.2 ?? Or something along those lines? Or is that completely wrong?

    And how do these IU/ml values fit in?


    My own lab virus antibody tests use all three of these units of measurement:

    Cytomegalovirus (IgG) Positive 7.0 IU/ml (Pos = > 0.4)

    Varicella Zoster (IgG) Positive: 1395.0 mIU/ml (POS = > 160)

    HSV-1 (IgG) : Positive: Index = 4.212

    Epstein-Barr virus:
    EBNA IgG antibody High Positive : 3.383 OD ..... (Pos = > 0.350)
    EBV Early Ag ab.(IgG) Negative : 0.250 OD ..... (Neg = < 0.350)
    EBV Early Ag ab.(IgM) Negative : 0.081 OD ..... (Neg = < 0.350)

    Herpes Six:
    HHV-6 IgG Ab. [By IFA] = Titre of 1:160
    HHV-6 IgM Ab. [by IFA] = Titre of 1:20


    I love to clear this up, and have the rule for conversion between these titer measurement systems.
  4. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Hi Hip,

    I too am interested.
    With the cmv range, was the >.4 positive, was a reference given by the lab u got tested at??
    My test done after 6 months on famvir showed my cmv IgG at 1.03 but doesnt say what measurements were used or even a reference range, just says positive to past infections, i assume its same measurements used as your cmv test. At this time of testing my lymphocyte sub sets were elevated and especially cd8 which is common in cmv.

    cheers!!
  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Just read something that says even with elevated igg and igm titres the patient still has to be symptomatic and is only a concern in immunosupressed people, so doesnt sound very accurate if at the end of the day they go by symptoms?? It seems a very gray area. It seems that titres are a way of measuring if a treatment is working or not, i think?

    What does the test result mean?
    Care must be taken when interpreting the results of CMV testing. The doctor evaluates the results in conjunction with clinical findings, including signs and symptoms. It can sometimes be difficult to distinguish between a latent, active or reactivated CMV infection. This is due to several reasons, including:

    A healthy person who has been infected with CMV at one time will continue to harbor the virus. The CMV can reactivate intermittently, often sub-clinically, shedding small amounts of virus into body fluids but not causing symptoms.
    An immune-compromised person may not have a strong antibody response to the CMV infection their IgM and IgG levels may be lower than expected even though they have an active case of CMV.
    The virus may not be present in sufficient number in the particular fluid or tissue tested to able to be detected.

    http://labtestsonline.org/understanding/analytes/cmv/tab/test

    Maybe this is why treatment trials are recommended by cfs docs. Montoya recommended av's for cfs patients with a sudden viral onset of their cfs, not just viral testing. It seems that testing isnt very accurate to tell the severity of infection but rather symptoms????
  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    immune compromised patients can show low titres even though having an active infection, interesting??
  7. snowathlete

    snowathlete

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    http://virology-online.com/presentations/index.htm in this link is a slide about herpes virus, what was interesting was that it said that IgG antibodies for cmv only have to be present for virus to reactivate in immunosuppressed patients. I havent read it all yet but assume it also occurrs in ebv and hhv6 etc

    I expect that alot of viruses affect us more easily than normal people. So, a 'normal' range becomes problematic IMO. I think they are helpful to put on the roadmap (great work everyone for finding all the stuff you have so far) but if you were borderline, or even low, i would still be tempted to take the antivirals.

    Unless they are dangerous to take, which one of them is from what i have heard, and if they are afordable, then why not take them and see if it helps. As Montoya suggests, they may be helping in other ways anyway. Who is to say there isnt a new herpes virus involved that hasnt been discovered yet, for example.

    Trying something beats doing nothing and waiting to die, which is what the NHS in the UK want you do (in my experience anyway).
  8. searcher

    searcher

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    snowathlete- I agree that the titers do not seem to be accurate indicators in many cases of whether we have an active infection, since we seem to re-active viruses even when our IgM isn't positive. I think that is why we are in a tough position convincing doctors to trial antivirals- since diagnosing an active infection in a CFS patient requires clinical judgment, then only a doctor who has experience with CFS patients understands how to interpret all of the test results and the symptoms to determine whether antivirals are warranted. Since not many doctors spend the effort to learn more about CFS, then we are stuck seeing one of probably only 10-20 doctors in the US who have experience. And we have a delayed response to antivirals, so the trial has to go on for months before we know if it is having a positive impact.

    Does anyone know if Montoya et. all published any of their data on the double-blind study? There is good info in the paper I posted, but it's only data for 12 patients and it would be great to have more examples of activity levels of patients who take a course valcyte correlated with pathogen test results.

    Also, does anyone see Montoya and know what test results he looks for now to determine treatment course?

    Hip- I think the 4x rule is just to make sure the IgG titers are significantly higher than that in an average healthy control. I will see if I can find some more quotes from the viral experts. But the more I look, the more that "clinical judgment" is playing a significant part in diagnosing active infection, which makes it difficult to create a simple flowchart. I suspect the lead clinicians are following a relatively objective algorithm for diagnosis, but I am not sure if any of them have articulated it outside this paper.

    I think I mentioned this before, but I see Dr K and he prescribed valcyte to me and my IgG levels (other than parvo) appear to be like the healthy controls. So I am starting to think his algorithm may be:
    nk cell function<=10 (or similar) + cognitive and autonomic dysfunction indicative of CFS => prescribe valcyte
    nk cell function<=10 (or similar) + cognitive and autonomic dysfunction indicative of CFS + bed-bound => consider rituximab
  9. Tristen

    Tristen Senior Member

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    Thanks Hip, this graph is similar to the one on my lab results, but easier to interpret. It shows past EBV infection and negative for current active infection.

    Still interested to know if this Ab test would in any way be accurate for detecting active infection in bone or B cells. I would think one would still have some EA Ab's. Maybe not a lot, especially being immune compromised, but there should be some.
  10. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    In oslers web and the lake tahoe outbreak, dr peterson found patients who initially had life long igg antibodies to ebv that later on tested negative, i think this is because they were severly immunocompromised and couldnt make these antibodies. I wonder how many people with cfs test neg to these viruses but are having problems. Also shows that those whose docs say its just a past infection when they have igg antibodies only have to think twice, if viral symptoms are present then they could well be reactivating???
  11. Hip

    Hip Senior Member

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    I have not come across this concept of the severely immunocompromised not making antibodies before; it's very interesting. I know there are cases of secretory IgA antibodies being low in CFS patients, but I had not heard about low IgG.


    Though an alternative (or additional) explanation for a lack of IgG antibodies in CFS patients might be because their CFS is primarily driven by an enterovirus infection (and the EBV was a co-infection that was eventually brought under control). Since the non-cytolytic side of a enterovirus infection lives inside our cells, it does not evoke an antibody response. So with enterovirus you can be very sick, but without any significant antibodies present. The non-cytolytic infections are hidden away from the immune system and from lab testing.

    Even when you do an ARUP Lab coxsackievirus B / echovirus antibody test as a CFS patient, the antibody levels found are very small (compared to the levels found in an acute enterovirus infection, when you have loads of normal cytolytic enteroviruses everywhere). This is why only ARUP's very sensitive antibody test can detect them.

    Someone I know with CFS, who is being treated by Dr Chia, had these coxsackievirus B results from ARUP:

    ARUP Coxsackie B Virus Antibodies
    Coxsackievirus B1 positive: 1:40
    Coxsackievirus B2 negative: 1:10
    Coxsackievirus B3 positive: 1:20
    Coxsackievirus B4 positive: 1:160
    Coxsackievirus B5 negative: < 1:10
    Coxsackievirus B6 negative: < 1:10

    So I believe anything equal or above 1:20 is classed as positive (presumably meaning that the virus is present).

    I am not sure how Dr Chia interprets these values in order to work out whether what he calls a "smoldering" chronic enteroviral infection is present. Perhaps those who have been seen by Chia will have a better idea on this point.

    In other words, what is the threshold CVB titer level that indicates not just that the virus is present, but that a "smoldering" chronic enteroviral infection is present.

    Though I understand that the more definitive test is the stomach biopsy test for this smoldering infection.
    Last edited: Jul 13, 2014
  12. Hip

    Hip Senior Member

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    Thinking about it, my above enterovirus theory would still not explain how lifelong EBV antibodies could completely disappear. That is odd. And it does suggest IgG deficiency.

    I found these two webpages on IgG Deficiency:


    Primary Antibody Deficiency

    Immune Deficiency due to IgG subclass



    Another explanation might be that with this intense and epic long-term antiviral battle going on in the bodies of CFS patients, somehow EBV may have been completely wiped out by the immune system?? I don't know if that is possible. I guess you'd have to check to see whether or not the patient was making IgG antibodies to other viruses like HHV-6 and varicella. If no antibodies were made to these other viruses as well, then it would definitely suggest IgG deficiency.
  13. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Enteroviruses could lower immunity enough to stop immune system from making antibodies. I think any infection could possibly do this i guess. I also have had similar problems making antibodies to vaccinations. My last test for hep B antibodies showed i had no antibody titres to hep B at all which my doc said was very strange since i had done the course of vaccines and had an antibody response after this. Its hard to know which infection in cfs/me is the driving force but i think all have an affect on our immune response???

    cheers!!!
  14. searcher

    searcher

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    My doctor ran a total IgG and IgG subclasses test. I think it would be a useful test for CFS patients, but I don't get the impression they are run often for some reason. IgG 1 and IgG 3 are supposed to be low in some CFS patients (see http://www.ncbi.nlm.nih.gov/pubmed/12000020)

    In my case my IgG 4 was really low (a third of the minimum.) IgG 4 is primarily for respiratory infections. I used to get a lot of respiratory infections before I got really sick with CFS, but interestingly I haven't had a cold or flu in two years so I guess some other part of the immune system is dealing with the fight.

    I think any of the deficiencies will lead to lower IgG levels for specific viruses, so seems worth knowing. And there are treatments for these deficiencies, which may or may not be useful in CFSers.
  15. Tristen

    Tristen Senior Member

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    I've also heard that we don't form/maintain Ab's to vaccines as well as other folks. But measuring to what extent it's true would be very difficult since a significant percentage of the healthy population don't either. (This is only one factoid against the erroneous claims that those not vaccinating are to blame for the return of certain infectious diseases. But that's another issue).

    I don't have Ab's for CMV, and yet had a raging active infection.

    My IgG subclass panel is normal.
  16. searcher

    searcher

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    Tristen- When you say you don't have antibodies to CMV, do you not have any IgG or IgM for CMV but have the virus in your blood? Or do you have IgM and not IgG? Just curious as to how our weird immune response manifests itself in tests.
  17. Tristen

    Tristen Senior Member

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    Both IgG and IgM are negative (Labcorp). Positive by Culture and DNA Nested PCR (WVRG).
  18. searcher

    searcher

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    Wow. I don't have CMV antibodies but didn't realize I could be positive by culture. This makes the testing flowchart even more difficult since doctors can't depend on the antibody tests.
  19. Tristen

    Tristen Senior Member

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    The other CMV Ab testing I've done over the years have been negative too. Wasn't until I did this DNA & Culture testing that it showed up.

    WVRG is also doing this kind of testing for other HHV's, but I'm always negative on those. My understanding of HHV6 is that it's a stealth virus sometimes requiring multiple tests to catch it. I'm always negative on that one. I want to do their EBV DNA test. http://www.wisconsinlab.com/test_list.htm
  20. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Ditto on HHV6. I know several who were negative on antibodies but it was found in abundance by PCR.

    Sushi

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