New Atmosphere, New Vision: Gibson and Whittemore Kick Off Invest in ME Conference 2016
Mark Berry reports on Dr. Gibson's introduction and Dr. Whittemore's keynote speech, at the 11th Invest in ME International ME Conference in London.
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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 wouldn't expect to have significant lymphocytopenia until the CD4 count gets lower. For example, this study was able to predict CD4 cell ranges from total lymphocyte counts in ART naive HIV patients. They were able to predict a CD4 range of 200-499 /uL from a total lymphocyte count of 1200-1500 /uL with a maximal sensitivity 96.67% and specificity of 100%. For total lymphocyte counts below 1200 /uL, they predicted a CD4 < 200 /uL with 72.2% sensitivity 100% specificity.

    The data I was referring to for significance was the CD4 %. Here is a bigger plot of the data so it's a bit easier to see.
    [​IMG]

    From the data you can see two clusters, the first four data points form one and the last 3 data points form the other. It is evident that the measurements are clustered around different means. So I can calculate the mean values for each cluster and I get the following:

    Cluster 1: 34.025 %
    Cluster 2: 29.7 %

    Now with these means I can calculate the probability that this shift indicates a statistically significant biological change rather than a change due to test analytical variation or individual biological variation using the reference change value method.

    [​IMG]

    Establishing a trend would be more prone to error given the underlying data is so limited. The main issue is that only one significant drop has been observed so far so it's not really possible to accurately estimate a trend until more are observed. But if I were to estimate a similar progression to what is seen in this data with a OLS linear regression, I get a p-value of 0.0247 from the t-test indicating that the slope is not equal to zero at p < 0.05.

    If I had to rank my chronic symptoms in order from affecting my quality of life from most to least I would say:
    • Joint degeneration (pain, crepitus, instability. mostly the knees and hips but others affected as well)
    • Chronic HPV infection
    • Lipoatrophy (pain, self-conscious of face changes)
    • Dry mouth
    • Dry eyes
     
    Last edited: Mar 30, 2017
  2. ukrmen

    ukrmen

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    Hi @ undiagnosed.
    Statistical analysis and, in particular, Student's test, works best for random variables that obey the normal distribution law, and in any case for stationary processes.
    Random measurements on sufficiently long time intervals can hardly be considered normal, and even more so stationary. Change of seasons of the year, types of nutrition, reagents, life situations, etc. You yourself see clearly two clusters of data when measuring the percentage of helpers.
    I will not argue about the correctness of the methodology and oppose you in this vein. My advice is this. Before initiating preventive antiretroviral therapy, do at least a couple of additional measurements of lymphocytes with a CD4 + marker at intervals of 6 months. Not critical is the small number of helpers you have. Look at my story.
    In any case, if there are additional data, and you want to share them, ready to discuss.
    Sincerely, ukrmen
     
    Last edited: Apr 2, 2017
  3. undiagnosed

    undiagnosed Senior Member

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    Sounds like you have a background in statistics. I basically agree with what you said. My main point was that a statistically significant drop was observed. Based on the limited data I don't think any model would be particularly good for trend inference statistics. If you have any recommendations for future investigation, I'd be happy to hear them.

    I am still trying to get access to the testing I mentioned previously and I really need to make something happen before the length of time that you mentioned. It looks like I may have an opportunity to get a sample analyzed for reverse transcriptase activity but I'll have to see how it plays out.
     
  4. undiagnosed

    undiagnosed Senior Member

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    It's been a while. I never did get a sample analyzed for reverse transcriptase activity primarily due to a number of logistical problems. However, I recently found an alternative option and I am now waiting on data from that analysis.

    In other news, it's been roughly 6 months since my last CD4/CD8 lymphocyte subsets were measured. The latest measurement shows the CD4 absolute count and percentage continuing to decline.

    [​IMG]

    The CD4 absolute count and CD4 % are both now below the reference range lower bound. Additionally, the WBC and lymphocyte counts are not below historical lows so the drop is due to a reduction in the CD4 %, not due to any top level changes in white blood cell counts.

    The image below shows a zoomed in plot of the CD4 % data for improved readability.

    [​IMG]

    As discussed in the prior post there were two clusters around two different means at 34.025% and 29.7%. The newest data point is significantly below the prior 34.025% and 29.7% cluster means. The probability that this drop represents a statistically significant biological change is calulated below using the reference change value method.

    [​IMG]
     
    Last edited: Sep 19, 2017
    ukrmen and vitaly48 like this.
  5. waif

    waif

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    this thread is amazing but also overwhelming

    what kind of doctor should i see to get this kind of extensive labwork? a rheum? i'm trying to get most of it covered by health insurance.

    thank you
     
  6. undiagnosed

    undiagnosed Senior Member

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    @waif, what tests specifically are you interested in? I've had to get most of these tests on my own through sites like Walk-In Lab and pay out-of-pocket.
     
    waif likes this.
  7. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    @undiagnosed I would urge you to check into vitamin A deficiency. I also had chronic HPV infection, dry eyes, numerous illnesses due to apparent low immune system since birth. What I finally discovered was a long term vitamin A deficiency. Vitamin A is known as the anti-infection vitamin. Without true vitamin A your immune system is very weak and rather wonky.

    Many overlook this possibility because they are taking vitamin supps which are said to contain vitamin A (but it is actually carotene - which converts poorly to vitamin A if at all. Many... estimated over 50% may not even be able to convert carotene to vitamin A due to common genetics.)

    Think you get vitamin A in your diet? No, it is not in plants. Many articles state various plants contain A but it once again they actually mean carotene, not true (aka preformed) vitamin A, but erroneously equate the two.

    Real vitamin A is to be found in the diet by consumption of certain animal products, the primary source being liver.

    Major consumption of vitamin A through beef liver has greatly restored my health. It finally allowed my body to kick the HPV infection which had progressed to stage 0 cervical cancer - I am now cancer and HPV clear. Dry eyes have become moist again and vision is better.
     
    sb4 likes this.
  8. waif

    waif

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    @undiagnosed i'm honestly not sure

    a hematologist ordered iga, igg, igm and those were normal but my c3/c4 levels are severely suppressed.
    i was referred to a rheum. i test negative on anything related to lupus, sjogren's...etc. and the rheum said some people just have chronically low c3 c4 levels for no apparent reason. but i have horrible peripheral 24/7 peripheral neuropathy in both my arms, gloved hands since 2010, which might even be brachial neuritis. i have a lot of stomach issues as well. i'm buying a 3day stool sample myself to test for pathogens. i had giardia for 2 or so years i believe bc my immune system is so supressed.

    i guess i need to find a really great rheum/immunologist. when i asked my rheum to test for viruses she basically changed the subject.
     
  9. TenuousGrip

    TenuousGrip Senior Member

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    @undiagnosed

    I could only read through about 1-1/2 pages of this.

    You're very smart and very well educated. That's a double-edged sword. DAMHIKT :)

    I saw others who mentioned that any number of more pedestrian (than HIV) viruses could explain your labs and symptoms. I totally agree. Many of your labs look a lot like mine.

    I actually think EBV reactivation could explain much/most of your clinical picture:

    https://www.cdc.gov/epstein-barr/hcp.html

    Also ... without knowing how much variability the average person has within those reference ranges you might be misinterpreting some of your lab test results. You may want to see what you can glean in that regard -- how much variability over time there is in some/any/all of those lab tests. My gut tells me that it's not unusual to bounce around within some SD of the mean over time.

    I also think you've assumed an even distribution across the reference range in the earliest analyses you posted on this thread. I think that needs to be validated too.

    I'd certainly recommend you get serology testing for the common viruses that are believed to be associated with ME/CFS (eg, the HHV viruses, m.pneumoniae, c.pneumoniae, etc.)

    Best of luck !
     
  10. undiagnosed

    undiagnosed Senior Member

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    @TenuousGrip, I respectfully disagree. If you have a chance to read the more recent posts I think you'll see that most of your points have been addressed. I'm not discounting possible co-infections, but I am confident that I am on the right path. I am currently working on a metagenomics investigation so we'll see how that plays out.
     
    pathogenunknown likes this.
  11. undiagnosed

    undiagnosed Senior Member

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    @Chocolove, I'll check it next time I go in for labs.
     
    Chocolove likes this.

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