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What about inherited immune deficiencies?

Discussion in 'Latest ME/CFS Research' started by richvank, Sep 19, 2012.

  1. richvank

    richvank Senior Member

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    Hi, all.

    I'm reposting this from another thread to give it more visibility.


    With regard to the discussion here about immune abnormalities in ME/CFS, what I would like to see is a study that looked for the most common inherited immune deficiencies in PWMEs. I think it is well established that there is immune dysfunction after a person has developed ME/CFS, but what I would like to see focus on is genetic abnormalities involving the immune system that people start out with.

    I think there has to be a reason why about 90% of people who get mononucleosis, Q fever, or Ross River virus (as in the Dubbo study in Australia) are able to recover, while about 10% stay chronically ill. And also, there has to be a reason why this 10% had more severe illness during the chronic phase. I suspect that these people started out with genetic abnormalities in their immune system, which prevented it from being able to ward off the chronic disease.

    There are many known inherited immunodeficiencies. I don't think very many PWMEs have been tested for them; and I think it would be instructive to do this. I have heard from a few who were found to have IgG subclass deficiencies, including IgG subclasses 1 or 3. I also heard from one person who was found to have mannose binding lectin deficiency. It is known that these deficiencies will make people susceptible to infections, and some of these people have been fighting infections since an early age. Some have had tonsillectomies at early ages because of persistent throat infections.

    As many of you know, I am the proponent of the Glutathione Depletion--Methylation Cycle Block hypothesis for the pathogenesis and pathophysiology of ME/CFS. This hypothesis describes the process of onset of the disease mechanism and the abnormalities in the physiology after the disease is established. So far, it does not deal in detail with the etiologies or root causes of ME/CFS, except to list the general categories of them, one of which is called "biological stressors" and includes infectious pathogens. I would like to extend it by developing a better understanding of how these pathogens interact with the immune systems of the people who eventually develop ME/CFS.

    As far as I can tell, the GD-MCB hypothesis is continuing to hold up with regard to the aspects of ME/CFS that it describes, as more research is being done, given that I have had to make a few changes and additions to it over time as more has been learned about ME/CFS.

    I think it is becoming increasingly likely that the "trip wire" for developing ME/CFS in most cases is the depletion of glutathione. If this is true, then the genetic factors that will matter are those that either inhibit the ability to make or recycle glutathione, or those that foster ongoing oxidative stress, which tends to deplete glutathione. In autism, which shares a lot of its biochemical abnormality with ME/CFS, certain genetic polymorphisms in the glutathione system have been found to increase the risk of developing autism by a factor of 4 (400%).

    One of main depletors of glutathione is the oxidative stress that is part of inflammation, which is produced by the immune system in response to infections. If there is an inherited immune deficiency that prevents successful elimination of the infection in the usual amount of time, the inflammation will persist, and over time I think that the accompanying oxidative stress will tend to deplete glutathione. This would be especially true if the person also had certain polymorphisms in enzymes affecting glutathione synthesis or recycling.

    So I think that looking for inherited immune deficiencies would help us to understand why some people get ME/CFS, while most others, subjected to the same infectious diseases, do not.

    While knowing this might not lead directly to treatments, I think we have to find out the basic causes of ME/CFS before we can know how to try to treat it.

    I would appreciate comments on this, and especially would like to know if any of you have had any inherited immune deficiencies identified, or if you have had infections more or less continuously since an early age, or if you had a tonsillectomy at an early age.

    Thanks.

    Best regards,

    Rich
  2. Enid

    Enid Senior Member

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    Thanks as always Rich - inherited immunodeficiancy probably yes - what overwhelms at ages 60ish in our cases (brother and cousin) - what weakness from sound good health tips the balance allowing (in my case expression of latent viruses suddenly and out of nowhere except a simple indication - sore throat and glandular swellings).

    But I stiil see only as a predisposition when for some reason the immune system - weak is overwhelmed. Never before - why ?.
  3. warriormom

    warriormom

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    In my children's case, they both have had ongoing complications from rheumatic fever that I am convinced predisposed them to CFS/ME. RF is on both sides of their family tree.
  4. Ema

    Ema Senior Member

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    I am deficient in IgG subclass 3 and in the bottom 4% for subclass 1.

    I'm trying to get Hizentra approved but having trouble with insurance coverage so far because I am only below range in one subclass.
  5. Marco

    Marco Old blackguard

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    Just to balance the discussion I don't have any history of frequent infections in fact my medical records show that for the ten years prior to ME/CFS I didn't have cause to visit my GP on a single occasion.

    However there is a strong history of inflammatory type conditions in my immediate family including fibrositis, COPD, anxiety, depression, cancer and of course ME/CFS.

    Oxidative stress of course by itself can cause reduced NK cell function and hence less resistance to opportunistic infections.

    So I doubt inherited immune deficiencies are ubiquitous but may be one of a wide range of 'stressors'.
  6. Aileen

    Aileen Senior Member

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    Until I got a certain flu-like illness, I was very healthy. I rarely even got a cold as a kid. The only infectious disease I ever got was from the vaccine and my first ear infection was at 15 years of age! No idea what happened but I doubt this theory applies to me.
  7. richvank

    richvank Senior Member

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    Hi, all.

    Thanks for the posts, and I hope others will keep them coming.

    It may be that we will be able to identify a subset that does have inherited immune deficiencies, another subset that had a serious acute exposure to a toxin, and others as well.

    As you may know, in the GD-MCB hypothesis, I have suggested that the stressors that apparently lead to the onset of ME/CFS in various cases include physical stressors (such as trauma, surgery and extreme exercise, as in the "overtraining syndrome"), chemical stressors (pesticides, organic solvents, heavy metals, and others), biological stressors (infectious pathogens, vaccinations, diet deficient in essential nutrients, lack of sufficient sleep, blood transfusions and others), and psychological or emotional stressors (death in family or of close friend, ongoing conflicts, divorce, abuse, dilemmas, and others). This is based on the "risk factor" studies that have been published, which in turn are based on interviews with PWMEs and normal, healthy controls. In many cases, it appears that more than one or even several of these various types of stressors were present simultaneously, and even though they may be quite different from each other, they are able to add together because of their common effect on glutathione depletion.

    I do suspect that there may be a substantial subset that started with inherited immune deficiencies, but I agree that that is likely not true for all cases. I think that one of the difficulties historically in ME/CFS research has been the attempt to identify a single root cause. My current view is that there is not one single cause, but there is a single pathophysiology that all the causes lead to, and that pathophysiology involves the vicious circle comprised of glutathione depletion, a functional B12 deficiency, a partial block in the methylation cycle, loss of folates from the cells, and draining of the sulfur metabolism.

    I think that treating the pathophysiology with methylation protocols has been successful in many cases, but it is still necessary to identify the root causes, some of which also need to be treated specifically. That's why I'm now trying to understand these better, and I think that inherited immune deficiencies are an important factor in at least a subset.

    Best regards,

    Rich
  8. Guido den Broeder

    Guido den Broeder *****

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    Rich, what makes you expect that these genetic abnormalities (which I agree we should be looking for) are inherited?

    Cheers,

    Guido
  9. richvank

    richvank Senior Member

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    Hi, Guido.

    I think that the immune abnormalities in ME/CFS are of two types: inherited immune deficiencies and immune dysfunction that results from the GD-MCB vicious cycle, after the onset of ME/CFS. There is lots of evidence for the latter. I'm interested in finding out whether the former are important factors in making people vulnerable to developing ME/CFS.

    If you mean that genetic abnormalities may develop after a person is born, such as occurs in cancer, that's true, but they would occur in isolated cells, and not be a characteristic of all the cells in the body, and would likely not cause dysfunction of the immune system.

    I hope I am understanding your question. If not, hit me again! :)

    Best regards,

    Rich
  10. PhoenixDown

    PhoenixDown Senior Member

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    Fibrositis was just the waste-basket diagnosis used before the term Fibromyalgia was coined (in around 1988 I believe), with the ACR research criteria being arbitrarily whisked up in 1990.

    Did those relatives diagnosed with Fibrositis have visible inflammation or any positive inflammation tests?
  11. Marlène

    Marlène Senior Member

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    Hello Rich

    What a coincidence you post about this. I decided to ask my doctor to get tested for porphyria.
    FYI: I had my tonsils removed as well.

    Will send you a private mail with more details.
  12. richvank

    richvank Senior Member

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    Hi, all.

    I just want to note that I think that Ian Lipkin is right in the statement reported below:

    "While leaving the viral question open Lipkin
    suggested the bodies response to viruses may
    play a larger role than the viruses themselves.
    People with ME/CFS could be reacting abnormally
    to normal levels of a virus or a virus could kick off a
    chronic response and then completely disappear -
    leaving a dysregulated system behind."


    Inherited immune deficiencies would explain this very well, I think.
    They could very well lead to glutathione deficiency as a result of
    viral exposure, and that would result in the
    launch of the vicious circle mechanism described by the
    GD-MCB hypothesis. and hence, a "dysregulated system"
    left behind.

    Best regards,

    Rich
  13. justy

    justy Senior Member

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    Hi Rich, thnaks for continuing to search for clues and answers to this dreadful disease.
    My history is one of recurring constant infections from early childhood. Tonsilitis (quinsy twice by age 10) recurring lung infections,chronic bronchitis and many many bouts of 'flu' at a young age. Pneumonia twice, glandular fever at 13, measles at 38 (despite vaccination). Had my adenoids out at 8, tonsils at 11. Between the ages of 17 and 30 i had frequent bladder and kidney infections as well as the ubiquitous lung infections (i now have extensive scarring in one lung) In my mid twenties, just before M.E hit i developed stomach problems and then it was one gastric bug and flu after another (still ongoing)
    As a teenager my mum took me to the GP with yet another illness/infection. My mum asked the doctor what could be done with me, the GP laughed and said 'take her outside and shoot her!' he was right - it may have been the only way to put an end to it all.

    My eldest daughter - now 18 has been having recurring, severe tonsilitis for about seven years - including spells in hospital on iv antibiotics all 3 other children well. (she may have M.E)

    All the best, Justy
  14. Marlène

    Marlène Senior Member

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    I tend to agree. It is the mechanism they have to focus upon.
  15. Marlène

    Marlène Senior Member

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    hello Rich

    Inherited:

    My late grandfather, daughter of my uncle, my father, myself and my youngest son all have the same symptoms/illness

    My best friend, her sister, her mother are all ill.
  16. Marlène

    Marlène Senior Member

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    People with autoimmune disease like lupus have more antibodies against EBV which might be a similar case of inherited immune deficiency.
  17. Shell

    Shell Senior Member

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    I'm another one with repeat infections. I had my tonsils and adenoids out age 5 as an emergency op because they were so swollen they had blocked my throat.
    Went on to have repetive bronchitis (even had postural drainage) and chest infections - in and out of hospital with asthma and infections.
    Had mild whooping cough and had rubella (so never had vac as I've got antibodies)
    Had mono twice aged 7 and something like 11 or 12.
    If it was going around - I got it.
    But I did go through a phase of being pretty well until this started 10 years ago. Even the asthma was so under control I wasn't using anything at all.
    Not sure there's much family history of this sort of thing though - it was just me.
  18. LisaGoddard

    LisaGoddard Senior Member

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    Hi, I haven't had any genetic tests but the three bouts of chronic fatigue that I have had were after infections. The first was after horrible tonsillitus when I was about 10 years old. I wish they had taken my tonsils out but the received wisdom at the time was to leave them in. I even dream of having my tonsils removed because they and my general throat area have been sore for the last two years following a routine cold virus infection. My ME which has persisted over the last 12 years has always involved pain in my lymph nodes.

    The methylation really is helping my energy levels, however, as I have gone from only being able to walk for 6 minutes every few days to 30 minutes daily.

    Still the inflammation symptoms persist so I will be interested to follow your thoughts Rich on this subject.
  19. ggingues

    ggingues $10 gift code at iHerb GAS343 of $40

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    RIP Rich, hopefully another angel will follow thru on this?

    GG
    Ema likes this.
  20. jewel

    jewel Senior Member

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    It would certainly be a tribute to him. I wonder if this forum could approach some of the well-known research entities with a request that they consider immune deficiency markers. It may be that the studies that have taken vials of blood from some of us could look into immune deficiency markers/patterns as well as looking at pathogens. Just a thought. Sigh...

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