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Surprises from my visit with Dr Rey

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by SOC, Apr 17, 2012.

  1. SOC

    SOC Moderator and Senior Member

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    Wow. Not what I was anticipating.

    First, my NK cell function is fine. That was really unexpected. Good, but unexpected. For me, the T-Cytotoxic/Suppressor CD3+CD8+ cells are the problem.

    My primary issue seems to be a mess of chronic infections which may be the reason for T-Cytotoxic cells being low. Now that I think about it, though, why do I have such a mess of chronic infections if my immune system wasn't messed up in the first place?

    I also have very low cortisol, so I have to get an appt with an endocrinologist ASAP. How could that not have been caught by now? D-3 is also low. Fixing just those two things could make a big difference.

    New infections discovered -- Parvo B19 and Coxsackie B2 (at least it's only one of the Coxsackies), so Equilibrant is the first thing I'll be adding.

    EBV Early Antigen is high, even though I'm taking a massive dose of Valtrex. We may switch to Famvir once I get settled in with the Equilibrant.

    No more HHV-6! So goodbye to Valcyte finally. It did a lot of good, but now it's time to move on.

    So, no Imunovir or inosine. We fight the infections directly and see if that gives my immune system enough of a break to sort itself out.

    That's a lot of info. My mind is still a little stunned by all the info.
    L'engle likes this.
  2. lnester7

    lnester7 Seven

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    SOC!!! I am so happy for you that at least you know what is wrong! it makes all the difference in the world so one can fight back!!! Good luck w new protocol.
  3. SOC

    SOC Moderator and Senior Member

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    Here's the out-of-range data from my immune tests. As I understand it, these abnormalities are indicative of immune activation due to chronic viral infections. Some parts of the system are "exhausted" causing other parts to increase in order to try to compensate. Any other thoughts on this data?


    Stuff that's low:
    TNF beta
    TNF RI
    IL17
    IL23 -- very low
    T-Cytotoxic/Suppressor CD3+CD8+
    T Cells (CD3+) -- low percent, normal numbers
    Total CD5+
    CD4 Ancuor CD45RA+CD62L+
    CD8 Ancuor CD45RA-CD62L-
    CD8+CD95+

    Stuff thats high:
    IL1 beta
    IL10
    T-Helper (CD3+CD4+)
    CD4 Ancuor CD45RA-CD62L+
    CD8 Ancuor CD45RA+CD62L- -- high percent
    CD4+CD38+
    CD8+CD28+
    CD4+CD26+
  4. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    interesting and sounds positive too. Was it a nk function test or just a number test?? My nk numbers are normal but function crap. Your sort of opposite to me with cd lymphocytes as my levels are high, not low. I cant find the exact paper but bond uni guys doing nk function study in cfs also found poor cd8 function as well, maybe something to look into.

    all sounds promising, good luck.

    cheers!!!
  5. SOC

    SOC Moderator and Senior Member

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    @inester -- Thanks! It's good to have things to attack, at least I don't feel helpless. ;)

    @heaps -- Both NK cell number and function were good. Odd that we are opposite in lymphocyte levels. I wonder if we'll ultimately be in different subsets of ME/CFS.
  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Are u able to explain your cd8 tests more, u have a few different kinds of cd8 tests, some are high and some are low. Checking over my tests it just says cd8 supressor cells, cd4 t helper cells and mature cd3 t cells. cd3 i believe are also a kind of nk cell along with cd56. Along with elevated cd8 i have always had elevated cd3 cells too, but my last to tests have been almost normal which i think has to do with famvir which have slowly brought it down.

    cheers!!!

    Tried to get u on chat??
  7. Adster

    Adster Senior Member

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    I'd love to know what sort of doc you'd have to see in Australia to get those tests, and what those tests are specifically called. It seems like you have some decent leads to work with there.
  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Any gp can order a lyphocyte sub set test, if they can understand it is another storie. The basics is that if the lymphocyte subsets are elevated indicated the immune system is fighting something and if low then the immune system is starting to tire, simplistic view, also cd8 lymphocytes are commonly elevated in ebv and cmv infections.

    The nk function test in australia was done by bond uni in a research study of cfs, not available outside of that, although the study is over now i did ask them how much it would cost to get this test done privately, they said they wont do it outside of research studies, bugger, otherwise go to the states to get the nk function test done??

    cheers!!!
  9. Adster

    Adster Senior Member

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    Thanks heaps, Heaps :)
  10. lnester7

    lnester7 Seven

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    Just a thought, you can order the tests from GP, then pay the GP to have a phone consultation with specialist for interpretation, The phone consultation was about US$200 for me. Maybe you can give your GP a list of tests and he can choose the relevant ones, as you have the phone consultation they can direct your GP the right track!!
  11. xrunner

    xrunner Senior Member

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    IL1b has a direct impact on the HPA axis. It may help your adrenals to understand the causes that elevates it. It's a shame that you don't have TNFalpha and IL6. These can also affect the HPA. Infections can drive this stuff, including non-viral infections.
  12. lnester7

    lnester7 Seven

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    SOC,

    Did she give a go on the NAD?

    7
  13. SOC

    SOC Moderator and Senior Member

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    Sorry I missed you!

    I'm pretty much flummoxed by the details, having no biology background. I've picked up a few things that your probably already know, but not much more. FWIW, Here are my notes:

    "Ancuor" is probably a typo on the lab report -- should be "Anchor"

    Stuff that's low:
    TNF beta (pro-inflammatory cytokine)
    TNF RI (pro-inflammatory cytokine)
    IL17 (anti-inflammatory cytokine)
    IL23 -- very low (anti-inflammatory cytokine)
    T-Cytotoxic/Suppressor CD3+CD8+
    T Cells (CD3+) -- low percent, normal numbers (immunoglobulin superfamily?)
    Total CD5+ (CD5 serves to mitigate activating signals from the BCR so that the B-1 cells can only be activated by very strong stimuli (such as bacterial proteins) and not by normal tissue proteins. CD5 was used as a T-cell marker until monoclonal antibodies against CD3 were developed.)
    CD4 Anchor CD45RA+CD62L+ (resting nave helper T cells?)
    CD8 Anchor CD45RA-CD62L- (memory cytotoxic T cells?)
    CD8+CD95+ (something to do with apotosis of cytotoxic T cells??)

    Stuff thats high:
    IL1 beta (proinflammatory cytokine)
    IL10 (anti-inflammatory cytokine)
    T-Helper (CD3+CD4+)
    CD4 Anchor CD45RA-CD62L+ (??? helper T cells)
    CD8 Anchor CD45RA+CD62L- -- high percent (effector memory cytotoxic T cells?)
    CD4+CD38+ (activated cytotoxic T cells?)
    CD8+CD28+ (CD28 is required for T cell activation)
    CD4+CD26+

    I think the extra info on the CD4 and CD8 cells tells us something about their activation.

    Do not take my word for any of this -- I'm still trying to figure this out and am not sure I'm going to be able to no matter how hard I try. :D
  14. SOC

    SOC Moderator and Senior Member

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    My TNFalpha and IL 6 are in the normal range.

    In what way does IL1beta have a direct impact on the HPA axis? Sadly, nothing in my notes from the doc tells me about IL1beta. I'm still doing a very crude internet search to see if I can understand the causes of these abnormalities. The simple answer I got from the doc is that my results are indicative of my body fighting off chronic infections for a long time. (Is that redundant?)
  15. SOC

    SOC Moderator and Senior Member

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    :D Erm..... sorry 7, when she said no NK cell dysfunction so no Imunovir, the whole NAD thing fell out of my mind, so I forgot to ask.
  16. Wally

    Wally Senior Member

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    SOC,

    Do you have the NK Cell Function count for the lab tests that are now within a normal range, as well as the count from when it was low/abnormal? Would you be willing to share this information? If yes, would you also be able to share what lab was used for testing? Thanks.

    Wally
  17. SOC

    SOC Moderator and Senior Member

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    These were my first immune tests and NK cell function was normal, so I don't think (or have no evidence) that it was every abnormal. The doc said that some people with ME/CFS have low NK cell function while others have low cytotoxic T cells. I'm in the second category.

    All my immune labs were done at the Immunology Lab at the University of Miami School of Medecine
  18. lnester7

    lnester7 Seven

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    SOC, Don't worry!

    I have both: low NK cell and Low T cell (high B cell).
  19. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Investigation of Lymphocytosis

    --------------------------------------------------------------------------------

    Introduction
    Lymphocytosis or increased blood lymphocyte count is common and occurs at some time in most people, usually in association with viral infections. The major causes of lymphocytosis are listed in Table 1. Lymphocytosis is commonly short lived, and investigation of such cases by immunophenotyping is usually unrewarding. Uncommonly. lymphocytosis may indicate a lymphoproliferative disorder. This is more likely if one or more of the features listed in Table 2 is present, in which case investigation by immunophenotyping is warranted..

    Analysis of Lymphocyte Subsets

    The first step in the investigation of lymphocytosis is to assess the major lymphocyte subsets: T cells, B cells and NK cells. The T cells are further divided into CD4 T cells (helper cells) and CD8 T cells (cytotoxic cells). An anticoagulated blood sample is required, and the preferred anticoagulant is acid-citrate-dextrose (ACD). The test should be performed within 24 hours of collection, because cells may deteriorate on longer storage. In the laboratory, small quantities of blood are added to tubes containing different antibodies labelled with fluorescent dyes. The tubes are then run on a flow cytometer, and the proportions of cells stained with the various antibodies are determined. In a healthy person, roughly 70-80% of lymphocytes are T cells, and approximately equal proportions of the remainder are B cells and natural killer (NK) cells. Of the T cells, the ratio of CD4 to CD8 cells is normally about 2:1. A full blood count tube must be collected at the same time, to determine the absolute lymphocyte count. The absolute counts of the various subsets are then calculated, and these values are usually more informative than the percentages. In children up to 6 years of age, the absolute lymphocyte count is significantly higher than in adults, and the absolute counts of the various subsets are also higher. .

    Infections

    In viral infection, the elevation in total lymphocyte count is caused by an increase in the absolute count of CD8 T cells. This occurs most dramatically in Epstein-Barr virus infection, but is also associated with other viruses such as acute CMV infection. The cytotoxic CD8 cells are able to kill infected cells, thereby limiting the dissemination of the virus. The CD8 count may remain markedly elevated for many months after the patient recovers. Other infectious diseases that may cause lymphocytosis include toxoplasmosis, in which CD8 T cells are selectively increased, and pertussis, in which all subsets are increased. However, in many infections the blood lymphocyte count remains within normal limits.

    Disorders of the Spleen

    Patients who have undergone splenectomy, or whose splenic function is otherwise reduced, may have a lymphocytosis. All lymphocyte subsets may be increased, especially NK cells, and the lymphocytosis itself is not clinically significant.

    Lymphoproliferative disorders

    The most serious cause of lymphocytosis is a lymphoproliferative disorder. If the clinical notes indicate that such a disease is suspected, and immunophenotypic analysis is requested, the laboratory tests the blood sample with a large panel of antibodies, to determine whether the lymphocytes have abnormal markers, and whether there is evidence of monoclonality.

    i. B cell lymphoproliferative disorders

    All mature B cells express either kappa or lambda antibody light chains. In a normal individual, there is a mixture of kappa and lambda B cells. In a neoplastic disorder, with a monoclonal population derived from a single B cell, there is a predominance of either kappa or lambda cells. The test for kappa and lambda is simple and reliable.

    B cell chronic lymphocytic leukaemia (B-CLL) is by far the most common lymphoproliferative disorder associated with lymphocytosis. B-CLL is usually slowly progressive, and in many patients, abnormal cells can be detected in the blood well before the development of symptoms and signs. It is increasingly common for B-CLL to be first suspected when an incidental lymphocytosis is noted in a full blood count. A minority of cases of B cell lymphoproliferative disorder with lymphocytosis are B cell non-Hodgkin lymphoma (B-NHL). (In this condition, even if the total lymphocyte count is not elevated, the abnormal cells can sometimes be detected in the peripheral blood.)

    Once a monoclonal B cell population has been identified by kappa and lambda analysis, various other markers are used to distinguish between B-CLL and B-NHL (Table 3). In patients with a lymphocytosis, if the phenotype is consistent with B-CLL, a diagnosis of B-CLL can be made without further investigations, provided the blood film morphology and clinical features are consistent. Immunophenotyping can also confidently identify B-NHL cells, and provide initial clues to classification. However, there are many different subtypes of B-NHL, and full diagnosis depends on a tissue biopsy.

    ii. T cell and NK cell lymphoproliferative disorders

    CD4 T cell, CD8 T cell and NK lymphoproliferative disorders are much less common than their B cell counterparts, and classification is less satisfactory. It may be difficult to distinguish a reactive lymphocytosis from a lymphoproliferative disorder. If an elevated T cell count is detected as an isolated finding in an otherwise healthy individual, the lymphocyte subset determination should be repeated every 3-6 months. If the condition is post-infectious, the T cell counts are likely to fall gradually; increasing counts favour the possibility of a lymphoproliferative disorder. Immunophenotyping can detect monoclonality in about half the cases of CD4 or CD8 T cell lymphoproliferative disorders by specialized methods.

    http://www.sydpath.stvincents.com.au/tests/ImmunoFrames/lymphocytosis.htm
  20. SOC

    SOC Moderator and Senior Member

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    Thanks, heaps!

    As far as I can tell, my total lymphocyte count is fine -- 1.564 where normal range is 1.000 - 4.200

    Where is seem to be messed up is in the CD4:CD8 ratio. The above source suggests it should be about 2:1. Mine is about 6:1. I also appear to be somewhat low in T cells relative to B and NK cells. My looks like about 66% T cells, 15% B cells, and 15% NK cells. (I know it doesn't add up to 100%, but I'm not sure where I'm missing something. Even if the missing 4% are T cells, I'm still at the very bottom of the 70-80% range.)

    Not sure what that all means, though.

    ETA: The little I can find suggests a high CD4:CD8 ratio can be associated with autoimmune diseases (no surprise) and Hodgkin's Lymphoma. With a family history of HL (grandfather, uncle, cousin and maybe more), this is not encouraging.

    Maybe if I keep beating on this, I'll come up with some information I can understand. **sigh**

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