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Study finds Igenex has a 57.5% FALSE positive rate - I'm horrified!

Discussion in 'Lyme Disease and Co-Infections' started by cyclist, Feb 21, 2017.

  1. cyclist

    cyclist

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    Hi Gang!

    I was at a in-person lyme support group meeting a couple weekends ago and someone shared this study with me...
    It was published Sept 2014, by Brian Fallon at Columbia University, (who has a good reputation in Lyme community) -- AND it found that Igenex has a 57.5% false positive rate among 40 healthy volunteers. These were normal healthy people! I am horrified! Table 2 shows the false positives, and "Specialty Lab B" is Igenex.

    It also appears that Igenex responded almost a year later, in the pubmed commons section under the abstract. I find their response disturbing, on multiple levels.

    https://www.ncbi.nlm.nih.gov/pubmed/25182244

    I am very upset. Extremely. Upset.

    What do all y'all know about this? Any info would be greatly appreciated.
     
    Last edited: Feb 22, 2017
  2. Helen

    Helen Senior Member

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    Sounds really bad if they´ve fooled their customers. In March, if it goes as planned, a Finnish group of researchers will make a reliable test available ( I have talked to two doctors about it, and they were quite excited). Here is a link to the site about the test:
    http://www.tickplex.com/

    I was told that the test will be available in Finland, Germany and in the US.

    Edit: the test was discussed in this thread
    http://forums.phoenixrising.me/inde...ave-lyme-disease-without-knowing.49166/page-3
     
    Last edited: Feb 22, 2017
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  3. Belbyr

    Belbyr

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    Hi, I might be doing something wrong. Where does it show the healthy controls results and where is Igenex's response?
     
  4. cyclist

    cyclist

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    @Helen - yes, this is very concerning as most ILADS doctors in the US are ordering Igenex testing. Thank you for the links regarding tickplex. I will most definitely look into this!

    @Belbyr - if you click through the pubmed link and then open the article in PDF, it's easiest to read the tables. The false positives are shown on Table 2. "Number and Percentage of False-Positive Serologic Test Results and Discordant Pairs for 40 Medically Healthy Controls"

    The column to the far right is "Specialty Lab B" which is Igenex. The last row heading is "+WB IgM or IgG (laboratory)", which means positive by Western Blot IgM or Western Blog IgG according to laboratory criteria. Under the Specialty Lab B (Igenex) column, you'll see that 23 of 40 medically healthy controls (57.5%) were positive for Lyme. These were medically healthy controls!

    As for the Igenex response, it is found under the the abstract in Pubmed (before clicking through to the article), in the "pubmed commons" section. Raphael Stricker posted it in conjunction with the owners of Igenex, on Nov 15, 2015. IMHO, it's a smoke screen about how great they are, and then 1 paragraph devoted to the issue at hand -- false positives. In this single paragraph, the logic from one sentence to the next is incomprehensible. It somehow appears they think it is appropriate to retest the samples at this stage (which it is not!) and it appears they are now using "revised interpretation criteria and recombinant antigen WB" to come up with another self-proclaimed specificity rate. Again in my opinion, there is a reason this was placed in the "pubmed commons" section -- and that's because no respectable peer reviewed journal would accept/publish something like this.
     
    ahmo likes this.
  5. Daffodil

    Daffodil Senior Member

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    Late stage/chronic Lyme patients often are not making enough antibodies though, right?

    40 is kind of a small sample, too....
     
    duncan likes this.
  6. TrixieStix

    TrixieStix Senior Member

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    @cyclist

    I myself just had testing done thru Igenex. My very reputable ME/CFS specialist had me do it. Since getting my results (doctor & I have not discussed them yet) showing a positive IFA and a strong "Igenex positive" IgM I have been researching this Lyme stuff myself.

    For me it's been helpful to learn about the known and accepted limitations of standard CDC testing. From a recent CDC post...

    "When performed and interpreted in accordance with current guidelines, 2-tiered serologic analysis has a sensitivity of ≈70%–100% and a specificity >95% for disseminated Lyme disease"

    This means there is up to 30% chance someone who is infected with Lyme will be negative via conventional testing. Of course if a person presents with an EM rash they will get a diagnosis and antibiotic treatment despite not testing positive.

    This brings us to the % of people who do not develop an EM rash. The CDC says that "approximately 70-80% of people with Lyme disease have EM." Some argue the % is lower.

    This leaves me to conclude that there has to be people who become infected with Lyme disease who never develop EM, and who also test negative on CDC approved 2-tier testing, and could I be such a person?

    My Igenex results show a positive IFA and I am positive for 7 different IgM bands . I know some in the ILADS camp would be quick to automatically declare that a screaming positive result, but I am taking a more guarded approach. I've been breaking down which of my positive bands are considered Lyme specific, and which are known to have cross-reactions as stated below in a NIH article about Lyme...

    "The numerous antigens present in whole-cell assays can result in cross-reaction with antibodies to other microorganisms or tissue components. Many diseases have been reported to cause significant cross-reactivity in IgM and/or IgG assays. Among such diseases are autoimmune disorders, Epstein-Barr virus infection, bacterial endocarditis, syphilis, other spirochetal infections, and Helicobacter pylori infection."

    So that's where I am at right now. For me I am glad to have been tested via Igenex as they test for more bands than is available via standard testing. In my case insurance covered the testing in full, and whatever the case turns out to be for me, given my symptoms and how Lyme-like rather than ME/CFS-like some of them are, I will rest more easily knowing Lyme disease was not simply excluded as a possibility based on standard testing that is known to have flaws.

    * And of course I didn't even get into the debate regarding IgM vs IgG in Lyme. The case for Lyme not seroconverting to IgG in some people seems to have some strong merit in my opinion, especially in those with immune deficiencies, etc.

    Also could my IgM just be showing evidence of an old infection that is not active? I do not know if it's possible to be exposed to get Lyme and clear the infection without treatment or not. Lots of questions to get answered. This from Dr. Bob Naviaux...

    "Third, latent and reactivated viral and bacterial infections can occur, but in the case of ME/CFS that has lasted for more than 6 months, this may be the exception rather than the rule. Some doctors and scientists have not done a good job at educating patients and other scientists about the difference between serological evidence of infection in the form of antibodies like IgM and IgG, and physical evidence of viral replication like PCR amplification of viral RNA or DNA, or bacterial DNA."

    I am assuming you have already been tested thru Igenex? Have you received treatment for Lyme based on your results?
     
    Last edited: Feb 22, 2017
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  7. TrixieStix

    TrixieStix Senior Member

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    I also plan on asking my doctor is she thinks getting the Igenex "31 kDa Epitope test" done would be worth it. Band 31 used to be thought of as Borrelia specific, but that is now known to not be the case.

    "The Lyme IgG or IgM 31kDa Epitope test is a qualitative immunoblot assay that determines whether the 31kDa band present on a Lyme IgG or IgM Western blot is due to B. burgdorferi specific antibody or not. B. burgdorferi specific epitope 31kDa antigen is denatured and separated by SDS polyacrylamide gel electrophoresis, blotted onto nitrocellulose membranes and cut into strips for the use of Lyme 31 kDa Epitope Test. It is known that Western blots, especially IgM, can give false positive results with some viral and bacterial infections. This test would be very useful to rule out those false positives."
     
    Last edited: Feb 22, 2017
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  8. Belbyr

    Belbyr

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    Ok I see it now. Yes, their response is a little unsettling. To me it sounded like, "Well 3 controls we didn't have enough blood to redo, so we threw them out" "A few more that we said were positive were actually negative" "After we redid the rest, more negatives" "Therefore we have 91% accuracy" Then... later, "Lyme testing is still innaccurate"

    Sounds like the people at Igenex are confused too.
     
  9. TrixieStix

    TrixieStix Senior Member

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  10. Belbyr

    Belbyr

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    If true, then my Igenex from 2007 must be outdated. You know of any more back and forth? Wonder if Fallon has made any comments, since...?
     
    cyclist likes this.
  11. Esther12

    Esther12 Senior Member

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    Thanks, I hadn't seen that response from them before.

    To me, it's looked for a while like IgeneX are dodgy money-makers, and that some alternative Lyme doctors like them because their testing has high rates of 'positives', so it makes it easier to sell 'treatments' to desperate patients.

    I've lost all my notes on this, but I think that this was the other paper which assessed IgeneX's testing and found it was rubbish: https://www.ncbi.nlm.nih.gov/pubmed/11182109

    Best wishes to anyone who feels that they may have been misled by some of this stuff.
     
  12. duncan

    duncan Senior Member

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    To better understand what might be at play here, it may be helpful to understand the history and market and political backdrops. There are plenty of books out there for those who might be interested and wish to invest the time. "Cure Unknown" by Pamela Weintraub comes to mind.

    There is a great deal of controversy surrounding some of the authors of the study you provided a link to, @Esther12 - arguably as much if not more as that purported to surround IgeneX. Perhaps this perception took root because they were so influential in supporting treatment recommendations as well as the 2T protocol, which some believe can miss as much as 30% of those tested. I suspect that probably many many more are tested with the 2T than IgeneX metrics. (incidentally, I think @TrixieStix was right in suggesting that IgeneX redid their diagnostic protocol - not sure when the last time the 2T was tweaked.)

    So if one is going to talk about being "misled" it may be good to understand there are two sides to that coinage. It is not a good thing if someone has Lyme and is told they do not, and accordingly receives no treatment; it is also not a good thing if someone is told they do have Lyme when they do not, and they receive unnecessary treatments.

    The bottom line is better testing would be good for most concerned.
     
    Last edited: Feb 22, 2017
  13. Valentijn

    Valentijn Senior Member

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    This study doesn't mention Igenex at all. Igenex requested that the authors of the study send them the samples which were sent to Lab B for analysis. There's no indication in Igenex's response that they are Lab B.

    It's also not clear when the samples were assessed, only that they were collected from 1999-2007. The tests they're assessing might not even be in use anymore.
    Could you explain why? The short-comings with the CDC's two-tier testing method are well-known, and even conceded by the researchers who developed those methods.
     
  14. Belbyr

    Belbyr

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    It looks like that was a 'LLMD' from California defending Igenex which is a California lab. Igenex was referenced in the link.

    As far as I know Fallon does not side with IDSA or ILADS. I've seen first hand lots of positive Igenex tests, even though the people that sent blood were perfectly healthy. This was the first stumbling block that started to cripple the clinic I received treatment at for supposed lyme.
     
  15. duncan

    duncan Senior Member

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    The same can happen with the conventional ELISA, and with the western blot. But the incidence of false negatives according to some may be higher for those vs IgeneX. Where is the outrage against that?

    Targeting a specific vendor seems somehow to miss the point that testing in general for Lyme - as well as other TBDs - sucks.
     
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  16. Belbyr

    Belbyr

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    Before Igenex there was Bowen labs. They had a 99% positive rate, so at least we are headed in the right direction. ;)
     
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  17. duncan

    duncan Senior Member

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    There are too many issues here to discuss fairly, so I will try to just lightly touch on three that appear salient and that my mind can summon readily.

    One is that this is in great measure a market conflict. Yes? This is about markets and market competitors in contention. The 2008 (?) suit levied against the IDSA Guidelines reflected that in part, I think.

    Second, some companies possibly serve a purpose in disputing the controversial narrative put forth by a couple of dogmatic agencies that Borreliosis is a little more than a nuisance disease. Many Lyme advocates feel - right or wrongly - that IgeneX is one of those companies. That this is an important conversation has little controversy.

    Third, there appear to be some appealing elements to IgeneX diagnostic offerings, including that they don't simply test the B31 strain - they use at least two. Also, they include one other virtually Lyme-specific band (or is it two?) the 2T does not -- these bands were removed from the usual WB due to the Lyme vaccine introduced 15 or so years back...but the bands are very Borrelia-specific.

    This gets very convoluted very quickly,and I am not at my best today. I am sorry for using that as a cop-out. A test such as mentioned by @Helen, or another direct antigen test like the Ceres nano (?) test - if validated - would be very helpful.
     
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  18. cyclist

    cyclist

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    Don't even know where to begin! I appreciate all the interest in the thread and all those who have taken time to participate! I will try to respond to as many as I can now (and more later if I don't get it). I must first learn how to reply w/ multiquote (appreciate your patience!).
     
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  19. cyclist

    cyclist

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    @Daffodil - I have also read that late stage/chronic lyme patients have impaired antibody production which may make testing antibody response more challenging. However, my understanding is that this has no bearing on FALSE POSITIVES, which is the concern being presented in this thread.

    Yes, I also wish the sample size was larger, but anything over 30 is worthwhile. And certainly with such a large error rate, this is most worthy of publication. Further, this part of the study (specificity/false positives) is fairly straightforward, and unless their is some grossly negligent sampling or selection bias, the results are provocative ... and disturbing.
     
  20. cyclist

    cyclist

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    @TrixieStix , I was not aware of that article, thank you for posting! This is exactly the type of information I was hoping to glean from this post. I will read it tonight with great interest. However, at this point, I will also view anything coming out of Igenex with skepticism. Prior to the Fallon study, Igenex was purporting excellent specificity -- which appears to have not been true. Otherwise, I wonder what your well-respected doc thinks of the Fallon study? Perhaps you can report back w/ any interesting insights.

    Yes, I tested positive on Igenex, and yes, I based treatment decisions on these results. I will now seek other labs for confirmation of results. I'm dying to know who "Specialty lab A" is ?!? Given their low false positive rate, I'd like to test with them...

    I appreciate your references to the NIH article and Naviaux, I have seen similar sentiment in my research as well. Nice to see another confirmation of these ideas.

    I wish you the best in sorting out your diagnosis and treatment path. Not easy...
     
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