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Undiagnosed Immunosuppression

Discussion in 'Immunological' started by undiagnosed, Mar 20, 2016.

  1. undiagnosed

    undiagnosed Senior Member

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    I might be able to convince my doctor to order a lymphocyte subset profile that would include counts for NK cells. That would still be useful, right? I'm not sure about the NK cell function, it doesn't look like the lab has that test. What type of doctor ordered that test for you?
     
  2. Kati

    Kati Patient in training

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    Hi @undiagnosed NK cell count is not going to be too useful as it is known to be normal for us oftentimes. It is the function or cytotoxicity that is know to be having a defect. It's like shooting a gun but not putting bullets in.

    I am not sure if you are in the US, but Quest has a test for it, it is time sensitive and must make it to the one lab in California within 24 hours of drawing.
     
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  3. undiagnosed

    undiagnosed Senior Member

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    Ok, thanks for the info.
     
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  4. undiagnosed

    undiagnosed Senior Member

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    Just thought I would post an update here. Over the last six months I've been monitoring CD4 and CD8 counts. The image below shows relevant graphs.
    [​IMG]

    My goal was to see if I could find any trend in the CD4 counts. I remain suspicious due to clinical symptoms and my relatively low CD4 numbers which all fall within roughly the bottom 10% of the reference population. The reference population mean CD4 percentage is 44.65%. My mean CD4 percentage is 34.03%. The reference population mean absolute CD4 count is 939 cells/uL. My mean absolute CD4 count is 544 cells/uL. In HIV populations, a CD4 count of 500 cells/uL is often used as the lower cutoff point for a healthy value. My latest CD4 count was 487 cells/uL which is below that threshold. With the limited sample size and variance in the data, I was not able to determine a statistically significant trend. I wish I had a CD4 count from about five years ago. Oh well...
     
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  5. undiagnosed

    undiagnosed Senior Member

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    Well, I'm still not really getting anywhere with doctors. The one slight improvement was that a few at least acknowledged that there is something wrong. However, they were unwilling to run any tests I requested. It's funny, pretty much every test I've had that demonstrates that there is a problem, I've had to order myself. Unfortunately my state doesn't allow residents to order their own lab tests so I have to drive to a bordering state and give a fake address. This is a pain in the ass as it's hours of driving and all paid for out of pocket. Also, the websites that provide this service only have a subset of the Labcorp and Quest Diagnostics tests available, so I haven't been able to get every test I wanted.

    I have what I believe is fairly convincing evidence suggesting HIV. If not HIV, it would appear to be an infectious agent with a similar pathogenesis. I wrote a paper here which is a summary of what I've been giving to doctors. I've been trying to get a reverse transcriptase activity test from various infectious disease doctors, but it looks like there's no way in hell that's happening. No commercial labs offer reverse transcriptase activity tests from what I can tell. The only other HIV test that I can get on my own is an HIV-2 proviral DNA test. I found a place that contracts with Quest Diagnostics, but the test is $599. That's very steep, but I'd be willing to pay it as there is still some uncertainty regarding HIV-2. Ideally though, I would prefer a test that is not dependent on specific DNA.

    If anyone has any feedback or ideas, let me know. The only other avenue I am pursuing at this point is to see an immunologist. However, there are none in my city so I'll have to travel and it will probably be months before I'll be able to see one. Also, I'm not particularly confident that would lead to anything as I strongly suspect this fundamentally lies in the realm of infectious disease.
     
  6. Sea

    Sea Senior Member

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    I've read that seronegative HIV is extremely rare. The lack of cases makes it very unlikely that this would be the answer for you given that you have associates that have developed similarly to you. Also making it unlikely is the time you have been unwell. Those with seronegative HIV usually progressed quickly to AIDS.

    You may however find some interesting reading in the seronegative AIDS research that could help you direct your testing to maybe discover what you have
     
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  7. undiagnosed

    undiagnosed Senior Member

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    Hi Sea,

    Ya, it is extremely rare, 25 reported cases as of 2010, a few more since then. As you pointed out, rapid progression is typical in those cases which my case does not fit. The only thought I had related to that was if it was seronegative HIV-2, maybe the progression wouldn't be as rapid, but would be rapid with respect to the typical HIV-2 long term non-progression. But then you have the fact that there's only been roughly a couple hundred reported cases of HIV-2 in the US.

    I am more suspicious of a novel strain that is too divergent for tests to detect or possibly even a different retrovirus. I don't really have a clue on the statistics for these scenarios. HIV tests have missed strains in the past and still do. They are continually updated to be able to detect the latest strains. I haven't seen any literature reporting how many cases were initially missed due to the test used not being able to detect the strain in question. There is an infographic here that shows the detection capabilities of some viral load assays. You can see most of the assays will miss certain groups or recombinant forms. Granted these aren't used for diagnosis but viral load monitoring. However, if you didn't have antibodies detected, you would be relying on one of these.
     
  8. Sea

    Sea Senior Member

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    When you say that you had a potential exposure to HIV do you know what it was that you were exposed to?

    My thinking would be to try to find a researcher interested in your case rather than doctors who have come to the limits of their knowledge of how to help you.
     
  9. undiagnosed

    undiagnosed Senior Member

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    No, due to the nature of the exposure I do not know what pathogens may have been involved and I have no one to ask to be able to find out.

    I recently saw a website called expertscape that looks like it could be helpful in trying to find a researcher. I guess the more difficult part would be convincing them to get involved. I'm also considering whether I should try to reach out to my state health department and/or the CDC.
     
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  10. undiagnosed

    undiagnosed Senior Member

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    I found an immunologist through expertscape who is not too far away (couple hours) and was able to get a referral. I have an appointment next month. He has a background in rheumatology and infectious disease as well as immunology. Although, I have not met him, I get the impression that he will be a good generalist with specialist knowledge which are the characteristics I am looking for. My hope is that he will look at all of the evidence and think critically about it. If he is in agreement with my hypothesis, I expect he would order the tests necessary to make a diagnosis. If he disagrees, I expect to be offered a differential diagnosis that fits that evidence and does not consist of "there's nothing wrong" or "I don't know". I hope my expectations are met.
     
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  11. undiagnosed

    undiagnosed Senior Member

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    I reached out to my state health department. They reviewed my data and gave me some feedback, but ultimately would not provide access to any further testing. They absolved themselves of responsibility, as is typical, by recommending I consult with an immunologist or infectious disease doctor. Infectious disease doctors haven't worked out. Still have a few weeks before the immunologist appointment. I attempted to get some more information on the HIV-2 DNA PCR available through Quest Diagnositics. I was able to get a little information but not much. Their assay targets the gag gene of HIV-2 and has a limit of detection of 100 copies/mL. They wouldn't give any detailed validation data so I'm not sure what subtypes were tested with it or characteristics such as the false positive rate. I did see one paper describing an HIV-2 subtype found in a US patient that was not detected by PCR for epidemic strains. The paper says an assay from Labcorp was used that targeted the gag gene. The Quest Diagnostics test may be vulnerable to the same problem, but data is not available to know for sure. However, I am leaning towards having the HIV-2 DNA PCR test done.
     
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  12. JES

    JES Senior Member

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    Is there a reason you suspect HIV over any particular virus? I assume you have been in close contact with a person who carries HIV shortly before the sickness period started? Otherwise HIV seems exceedingly unlikely, given the negative test results and the way it only transmits through close contact.

    CFS/ME patients are often documented with various immune deficiencies, which have nothing to do with HIV or any retrovirus. In tests on CFS/ME patients, a number of viruses have been identified, but there isn't a consistent pattern linking the disease to any certain virus. The strongest case is for enteroviruses, which Dr Chia have identified from stomach biopsies of CFS/ME patients (link).

    I have had a lowish WBC count and other slight abnormalities on a number of tests over the last 10 years, eye floaters, nerve pain, a constant feeling of sickness, etc. A very low ESR is also commonly found among CFS/ME patients on this forum, it is suspected this is due to hypercoagulation of blood. These are all common symptoms with CFS/ME and have nothing to do with HIV specifically.
     
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  13. undiagnosed

    undiagnosed Senior Member

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    The primary reason I suspect HIV over anything else are past and present clinical indications including Oral Hairy Leukoplakia and Generalized Lipoatrophy that are extremely rare outside of HIV infection, but common with HIV infection. There is a lot of uncertainty regarding the exposure itself other than, if present, transmission was possible. You can read my detailed rationale for further HIV investigation here if you are interested. It discusses lab tests, symptoms, and observations that I believe, when considered together, suggest HIV. I have not been able to come up with a more plausible explanation.
     
  14. undiagnosed

    undiagnosed Senior Member

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    One of the online lab testing services I use recently signed a contract with Quest Diagnostics and they were able to offer the HIV-2 DNA PCR test for less than half the price of the previously mentioned site, making it much more reasonable. I traveled last week to have the blood drawn for the test. I received the result and it was negative. Also, after months of waiting and hours of traveling, I had the appointment with the immunologist. I had high hopes, but unfortunately he was a waste of time. His diagnosis was that sometimes symptoms don't have any explanation and he thinks I have depression. I need to collect myself and come up with a plan.
     
  15. undiagnosed

    undiagnosed Senior Member

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    I just recently had my CD4 and CD8 subsets measured and have updated results. See the image below for the history.
    [​IMG]
    It is clear that there was a drop in the CD4 and CD8 percentages in the most recent result compared to the history of previous results. I wanted to examine whether there was any statistical significance to the decreases (represent real change in biological homeostasis, not due to analytical or biological variation). I applied a method called the Reference Change Value to look at this. This method is particularly suited to analytes that have relatively little intra-individual biological variation and more inter-individual biological variation. This is the case with CD4 and CD8 percentages. It also means using the reference range to identify abnormal values is not particularly accurate. This is because an individual can have values that are abnormal for them, but still lie within the reference range. You can read more details regarding the calculations in my updated paper here. The results were probabilities that the changes in CD4 and CD8 percentages represent real change in biological homeostasis. For CD4 percentage, the probability was 97.2% and for CD8 percentage it was 99.5%. Unless there was an unidentified lab processing error, the change does seem to indicate a physiological shift.
     
  16. Jammy88

    Jammy88 Senior Member

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    Hi undiagnosed,

    I'm not a Doctor - just a patient dealing with symptoms following an unknown infection I got in 2014. However, even though I don't know what you have, I'm sure your problem is not HIV. I invite you to focus your attention on other retroviruses and autoimmune diseases ( which are caused by infections). HIV testing is really accurate nowadays.

    Good luck and hold on,
    J
     
  17. undiagnosed

    undiagnosed Senior Member

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    Hey Jammy88,

    I agree that there are number of factors not suggestive of a typical HIV-1 infection such as:

    - Clinincally available HIV tests taken have been negative
    - CD4/CD8 not inverted, more than 5 years after infection
    - No Hypergammaglobulinema
    - CD8 counts aren't significantly elevated

    However, there are a number of factors that are suggestive of HIV infection such as:

    - CD4 % below referance range and appears to be decreasing
    - CD4 count < 500, not enough data to establish trend yet
    - Low T-lymphocyte proliferation by mitogen stimulation
    - Past Oral Hairy Leukoplakia lesion
    - Lipoatrophy, low Leptin
    - Arthralgia
    - Xerostomia
    - Suspected infectious agent (other people in close contact with similar symptoms)

    Going by known pathogens, HIV is the closest fit I can come up with. In any case, the types of analyses that I need for further investigation are research assays that would be sensitive to any bloodborne retroviruses, not just HIV. I am trying to get access to a broad spectrum virus detection assay such as the Virochip or VirCapSeq-VERT as well as a reverse transcriptase activity assay. However, in the US there are federal regulations against research labs without CLIA certification providing patient-specific results. So I'll need to find a way to work around that.
     
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  18. Jammy88

    Jammy88 Senior Member

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    Hi friend,

    If you get access to similar kind of tests, please let me know. Cuz I would be interested too.

    Thank you and best wishes
     
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  19. undiagnosed

    undiagnosed Senior Member

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    I've been doing a lot of waiting lately on requests that I've been sending out. Still haven't been able to find any researchers to work with yet. In the mean time, I figured I would try to quantify my concerns using probabilistic reasoning. HIV test results should be interpreted in the context of the test performance characteristics, transmission risk history, and symptoms. However, in my experience, doctors treat the test result as the only thing that matters and dismiss all other evidence. I created this paper to explore why that is an incorrect approach and can lead to incorrect conclusions. Specifically, I examined the probability of being HIV+ given a negative test result in the context of various transmission risk histories and symptoms. From the analysis, it is clear that symptoms can have a profound impact on the probability of being HIV+, even in light of a negative test result. I have more data to incorporate into the analysis, but it's a start.
     
    Last edited: Sep 16, 2016
  20. undiagnosed

    undiagnosed Senior Member

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    The graph below shows a sneak peek of something I've been working on that's an extension of the last post. I need to make sure there aren't any mistakes in the math, but you get the concept. It's basically taking what's qualitatively in my head and turning it into a quantitative analysis. I'll be updating the paper with all the math and statistics soon.
    [​IMG]
     

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