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Undiagnosed Immunosuppression

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

  1. undiagnosed

    undiagnosed Senior Member

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    Diagnosis of HIV is determined in the context of test results, transmission risk history, and symptoms. While HIV test results to date have all been negative, symptoms and secondary lab tests provide strong evidence supporting the HIV+ hypothesis. Using Bayesian inference, the probability of being HIV+ was calculated over time for each new piece of available evidence. Based on all of the evidence to date, the most recent probability of being HIV+ was determined to be 95.3%. The graph below shows the latest calculated probabilities which have changed a little from the last post due to some adjustments to some of the numbers.
    [​IMG]
    The latest probability of being HIV+ was calculated given the negative Oraquick ADVANCE result, negative Alere Determine result, negative Aptima Gen-probe result, negative Taqman 2.0 result, Oral Hairy Leukoplakia symptom, lipoatrophy symptom, CD4 < 500 result, shingles symptom, and risk history. The updated paper contains all of the calculation details. If anyone has skills in statistics and would like to review my work, I would appreciate it.
     
  2. undiagnosed

    undiagnosed Senior Member

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    Latest CD4/CD8 ratio results show continuation of depressed CD4% indicating that previous measurement drop was likely not an anomaly.

    [​IMG]
     
  3. Cohen2

    Cohen2 Senior Member

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    @undiagnosed Just have a question for you as you seem to have researched a lot. I recently had Lymphocyte subset done. Everything is in range but my CD4/cd8 ratio is 1.03. Do you think this could be a sign of a weakened immune system or ongoing infection? cheers
     
  4. undiagnosed

    undiagnosed Senior Member

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    Hey @Cohen2, I couldn't say without knowing more. Would you mind sharing the rest of your lymphocyte subset data? For most lab reference ranges I've seen you would be approaching the lower limit with that number. However, the CD4/CD8 ratio has a genetic component where some people naturally have lower or higher ratios. For CD4 and CD8 counts in general, the values due to biological variation for any individual only span a small part of the reference range. The reference range is so wide because between individuals there is a large variety of biological homeostasis set points. Therefore, in order to really know if that ratio was significant for you, you would have to know what your homeostasis set point was. Presumably you don't know that because you never had your CD4/CD8 ratio measured prior to your illness. So really you would need to consider your clinical history and any other tests that could indicate a weakend immune system or infection. You could also periodically monitor your lymphocyte subsets for changes if you had a strong suspicion that they are abnormal for you. I would only consider doing that if you had other evidence to warrant it.
     
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  5. Cohen2

    Cohen2 Senior Member

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    Thanks. My results were 1.7 lymphocytes
    Cd3 1.21
    Cd4. 0.61
    Cd8. 0.59
    Cd16 0.12
    Cd19 0.29

    HIV abs are negative
    Immunoglulins are in range

    I suffer from long lasting infections but they never can tell me what but no opportunistic infections that I know of. It could well be that I have low nk function like most with ME but I have no way of testing that in new Zealand.

    No way to know my set point as first time I've had subset. Lymphocyte count has varied between 1.2 and 2.2 over the last 8 years.
     
  6. undiagnosed

    undiagnosed Senior Member

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    @Cohen2, I plotted your CD4 % and CD8 % with a visualization tool I made. I posted it on the forums before and you can use it for one off lab result visualizations. I am going to be including this and other visualization tools as part of p2pdx when I get that up and running. The percentages tend to be more stable than the absolute counts which is why I used them here. I used the Labcorp reference ranges which are probably different from your lab, but you can run the tool again with the proper reference range numbers if you want. Here are the plots:

    [​IMG]

    [​IMG]

    The CD8 % is approaching the upper limit of the reference range and the CD4 % is in the bottom 10%. You said that you weren't sure what type of infections you are having. Are they respiratory? Sinus? Have you had your IgG subclasses measured? You could also consider looking to see if you have reactivation of latent HHVs such as CMV, EBV, etc? Not sure if you've done that. I've had minor opportunistic infections from EBV, VZV, but those were clinical manifestations. I haven't looked at antibody levels for any HHVs.
     
    Last edited: Feb 21, 2017
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  7. undiagnosed

    undiagnosed Senior Member

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    Unrelated to the prior post, I had some genetic testing done. One of the questions I have is whether host factors could be influencing disease progression. Besides negative test results, one of the pieces of evidence that is peculiar is that the CD4/CD8 ratio is > 1, 6 years post infection. Genetic alleles/mutations have been associated with slowed progression which in some cases could explain a CD4/CD8 ratio > 1. I had the HIV genetic resitance testing from PALFIR Genetics done. The results are shown below:

    [​IMG]

    None of the alleles/mutations tested for were found, so there was no genetic evidence for slowed progression. The alleles/mutations tested are not exhaustive but are the more studied ones. So given infection, either a different genetic source of CD4/CD8 > 1 or less pathogenic virus is implicated.
     
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  8. Lolinda

    Lolinda postprandial POTS + MCAS + beriberi

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    I found this paper useful:
    https://www.hindawi.com/journals/ad/2012/189096/
    "vitamin D.... mediated ... an increase in the number of CD8+ T cells available"
    take vit D to increase CD8+.
    I have low absolute numbers of CD8+, and I am supplementing as much vit D as I tolerate, hoping to improve it till a next test. (my goal is to control my active ebv, which is what CD8+ cells do. I was vit D deficient at the time of the wbc test below)

    - I have not read this thread from the beginning, so if this paper was already posted by someone, apologies!

    Questions to all:
    - do you have any ideas how to fix lowish absolute values of wbc? I just wonder if I could improve things a bit if I improved my slight wbc deficiency.
    - do deficiencies in terms of absolute numbers not just simply mean diluted blood?
    - anyone else tolerating only very little vitamin D? (no sleep + pulsation if I take more than 1500 iu per day)

    here my test results:
    IMG_20170224_073325.jpg
     
  9. undiagnosed

    undiagnosed Senior Member

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    @Lolinda, have you had this test panel done more than once? Did you have any acute illness when this test panel was taken? Are you taking any medications? If you had this degree of CD4 lympocytopenia on two or more measurements over at least 6 weeks, you would meet the criteria for idiopathic CD4+ lymphocytopenia, assuming there is no other explanation.

    There are possible treatment options to improve the WBC. It depends on if you can identify a cause though. The absolute numbers are calculated based on the total multiplied by the percentage. For example, your total lymphocytes are 1200 /uL. Your CD4 absolute count is calculated as 1200 /uL * 0.2 = 240 /uL. Your lymphocyte absolute total is calculated in the same way based on the percentage contributing to the total WBC. Your percentage isn't shown but we can calculate it as 1200 /uL / 4200 /uL = 28.6%. All of the calculations start from the top level WBC. So if your body is having difficulty producing WBCs, your totals for all subsets will be lower. You need to look at the subset percentage to see if you have an issue independent of the WBC total. For example, your CD4 absolute count is impacted in part due to the WBC total. However, the low CD4 percentage indicates an abnormality of that cell type independent of the WBC total count. Note that this is dependent on the reference ranges. Your CD8 percentage is in the reference range, but the absolute CD8 is low. That's a case where if the total lymphocytes were comfortably within the reference range your CD8 total would be too.

    ** EDITED to correct some statements **
     
    Last edited: Feb 24, 2017
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  10. sb4

    sb4 Senior Member

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    @Lolinda Problem with vitD supplement is it increases calcium absorption , if you have problems with calcium, as many of us do, this could cause your sleep problems.

    Best way to increase vitd is strong UVB sunlight, this skirts the calcium issue whilst irradiating your blood with all the spectrum of light white blood cells, red, enzymes , proteins , etc need to function optimally.

    I am trying to do this with artificial light as I live in uk however it's difficult.

    Do you live nearer equator ?
     
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  11. Cohen2

    Cohen2 Senior Member

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    Thanks for that. I think the infections are respitory mainly and last for a long time sometimes months/years. I havent had IgG subclass but my total IgG was around 9. So well in range. Once when my lymph nodes were swollen for a ,long time they took a fine needle aspiration and found a virus, I think it was a Rhinovirus. I think I will just wait and get a lymphocyte subset again in a year or so.
     
  12. Lolinda

    Lolinda postprandial POTS + MCAS + beriberi

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    Thank you so much, @undiagnosed for your attention. Yes, I had the test panel done 3 times: 2013, 2015 and end of 2016. I post them here in order of time. The one I posted above will be repeated here as the last one (from 2016).

    1st Test: 2013
    • Illness: I had CFS, essentially lots of fatigue. I was about to glide into ME, which I got some weeks after this test. I had some symptoms resembling NMDA receptor AB, meanwhile resolved. I had gut issues (diarrhea, intolerances, inability to eat enough, underweight BMI 18. Frequent flu-like episodes. Much in bed because of CFS. CRP and ESR absolutely normal.
    • Treatment: Nobody knew what I had, no diagnosis at that time, no medications.
    • Self-treatment: profited from a high fat low carb vegan diet. I did not tolerate any animal products except butter. I also tried to improve my situation by taking probiotics, which helped in the beginning, but as I noticed too late, they contributed to my progression into ME.

    2013-1.png 2013-2.png


    Test 2 in 2015

    • Illness: I already resolved my ME and CFS alltogether. I was still bed bound, however, much of the day. It struck me after meals that I had to lay in bed. My digestion was ruined if I stood up. I was able to eat meat again. Again I was without diagnosis, nobody understood my problem. All what was known was that I had an active EBV and that I have a chronic activation of the alternative pathway of the complement system (measured as diminished c3 but normal c4, several times). Progressive lower back pain that struck me together with flu-like episodes. Lower back pain meanwhile resolved. CRP and ESR absolutely normal.
    • Treatment: None
    • Self-Treatment: Ketogenic diet (High fat very low carb, much meat). This was what resolved my ME already in 2014 April and what I did since then. The keto diet I did not do for any neurological issues. I did not have any at that time. I did it to starve gut bacteria which I believed to be the cause of my trouble. Whe I re-introduce carbs, hell breaks lose symptom-wise, so I dont do that :)

    2015-1.png 2015-2.png


    Test 3 end of 2016
    • Illness: I am currently diagnosed with POTS, which explains why I cannot stand up after a meal (much blood needed in the belly which overwhelms blood flow regulation in orthostasis). While I could improve POTS for a while, by resolving a autoimmune component, meanwhile it is worse again, so bad that I spend most of the day in bed. Essentially I am bed bound. One single time two elevated autoantibodies found (ANA, ANCA) at other times none. Chronic activation of the alternative pathway of complement (meaured several times as diminished c3c). The EBV from 2015 was resolved in 2015, also I had an intestinal biopsy and essentially no viruses found, big panel tested. At the end of 2016 I had active EBV again, see below. I am diagnosed with demyelinating and axonal polyneuropathy: diminished feeling in feet, tingling, stinging pains (mostly resolved) hot or cold soles. All the time, from 2013 to now: almost no stomach acid (I supplement it with betaine hcl). CRP and ESR absolutely normal.
    • Treatment: None, all my many academic specialists have no clue.
    • Self-Treatment: I take lots of vitamins and minerals all transdermally: AGP Choline, Mg-Cl, Ca-citrate, Glycine, Alanine, B5, vitamin C, Chrome, Lecithin, Borage oil. They changed my life to the better in ways I couldnt believe before. I found out that via transdermal route I have no side effects. I was intolerant for all supplements orally. Here as an example my experiences with trandermal choline. Every day I do 1h of an intense physical training programm that helps against POTS.

    2016-1.png 2016-2.png 2016-3.png
     
  13. Lolinda

    Lolinda postprandial POTS + MCAS + beriberi

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    I hope it was ok to post all these details. Thanks @undiagnosed for asking precise questions. I like to answer them by precise answers :)

    Good point! So in view of the years, it looks like a constant decline of CD4 %:
    2013: 38% (31-59)
    2015: 28% (31-59)
    2016: 20% (31-59)

    Is this an established criterion? Certainly, I can search for references myself, I do have still my university access (I am a researcher). But in case you have a paper or link at hand, then pls post. Such things I found useful to catch the attention of immunologists and ask for further tests :)
     
  14. Lolinda

    Lolinda postprandial POTS + MCAS + beriberi

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    I checked this in historical perspective:
    Many years before any illness, I had multiple measurements of leucocytes in the range of 7.2, then 6.6 and here, above, you see values of 2013: 6.1, 2015: 5.1, 2016: 3.8 and 4.2. Looks like going down... In contrast, my RBC were always constantly at the lower normal limit in all tests ever done.

    So I am pondering wether all this is
    a) diluted blood (imo unlikely in view of RBC vs WBC trends)
    b) WBC are used intensively in the body (I guess they dont swim around in blood peacefully but run to sites of action, for example the gut (imo unlikely as no immune cells found in stool test)
    c) they die in fight :) (imo unlikely in view of my best possible CRP.)
    d) reduced production (my spectracell test went well, so my wbc do react to mitogens. though, I sent in 3 tubes in view of my low wbc count)
    e) production downregulated by some bad bugs
    f) defect / deterioration in the thymus...
    ... all the above is bare speculation, but mayb simply an effect of some years of disease (2013-now)?

    I also have an interesting finding: since 2010 it is known that my vitamin D always goes down badly if not supplemented. 30 min summer sunshine daily and 100g mackerel + 100g sardines every second day!! is not enough. Here comes a speculation that bad bugs are able to downregulate the immune system, in particular the VDR (I have research on that, if of interest )
     
    Last edited: Feb 26, 2017
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  15. kangaSue

    kangaSue Senior Member

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    @Lolinda Have you been assessed for any form of Vasculitis before? You mentioned above having had an ANCA antibody finding before and Vitamin D deficiency is highly prevalent in a lot of cases involving different causes of Vasculitis.

    A CT with contrast can pick up deformed vessels in some conditions.
     
  16. Knockknock

    Knockknock

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    Your case look like mine
    My onset was very similar, i didnt realized untill it became cronic 6 months later, do to a mycoplasma infection, as Jaime said infections especially active HHV6-EBV can cause more immune deficiency, especially lymphocyte.
    But the main root cause allowing infections to deplete lymphocyte is the low immunity, the NK CELLS.
     
    Last edited: Feb 26, 2017
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  17. undiagnosed

    undiagnosed Senior Member

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    Ya, I'm happy to take a look. I wish I had my project p2pdx up and running as it would make these exchanges and analyses much easier.

    Ya, I noticed from quickly looking over the records the decline in CD4 %, CD4 absolute, and CD4/CD8 ratio. I usually like to plot my data to help spot the more subtle trends. I'll try to plot some of your data and post it here afterwards.

    Ya, from this paper:

    Idiopathic CD4 lymphocytopenia (ICL) is a syndrome first defined in 1992 by the Centers for Disease Control and Prevention (CDC)1 as “a documented absolute CD4 T lymphocyte count of less than 300 cells per cubic millimeter or of less than 20% of total T cells on more than one occasion, no evidence of infection on HIV testing, and the absence of any defined immunodeficiency or therapy associated with depressed levels of CD4 T cells.”

    You could also take a look at the Wikipedia page for a quick overview.
     
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  18. Knockknock

    Knockknock

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    Jaja vit D, vit b12 and many others are desregulated do to mutation in the receptors, change in DNA.. something is changing our cells Dna transforming, do you know anything that does that?? Did you ever hear in any other illness something that enter the cell and copy and transfor DNA into a potter house ? Leaving people with out immunity!!!
    To me sounds familiar.. to you??
     
  19. Knockknock

    Knockknock

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    To me Lymphocytopenia its just a cover up, to shift the attention away from AIDS.. like they did with CFS...
    With clear hard evidence of immune deficiency and disfuntion CRONIC FATIGUE??? Really???

    Really?? Phsycological REALLY???
     
  20. undiagnosed

    undiagnosed Senior Member

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    Was 2013 the first year you were ill? If not, what was the first year?

    Well, there are definitely some things to rule out if they haven't been already. The obvious ones would be HIV-1 and HIV-2, which I'm assuming you've been tested for. Also, from the Wikipedia page:

    A one-time finding of low CD4+ cells is usually associated with a recent infection and resolves on its own.[7] Alternative explanations for the low CD4 counts include conditions such as blood cancers (aleukemia), treatment with chemotherapy, immunosuppressive medications, or other medications that suppress or kill T cells, infections, and problems with blood production.[1][8]
     
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