Possible effects of immune and detox genetic deficiencies on recovery

Discussion in 'Fibromyalgia Main Forum' started by richvank, Aug 12, 2012.

  1. richvank

    richvank New Member

    Hi, all.

    I’d like to comment on genetic deficiencies in the immune system and the detoxication system, and their possible influence on susceptibility to developing ME/CFS as well as their possible hindrance to recovering from ME/CFS.

    As many of you know, I have proposed the GD-MCB hypothesis for the pathogenesis and pathophysiology of ME/CFS. This hypothesis suggests that a variety of types of stressors can be involved in causing the onset of ME/CFS in a person who is genetically predisposed.

    The details of the genetic predisposition have not yet been completely elucidated. We know from a variety of types of evidence that there is a genetic component, though, including twin and family tree studies and polymorphism frequency studies.

    Two of the more prominent classes of stressors that appear to be involved in the onset of many cases of ME/CFS, based on patient histories, are infections by various pathogens, and intoxication by various types of toxic substances.

    I suggest that in the cases of people whose onset involved infections, there may be inherited genetic immune deficiencies that made them more susceptible to these infections. Some of them might be IgG subclass deficiencies or mannose binding lectin deficiency. There are no doubt other possibilities as well. In studying histories of PWMEs, I often find that they suffered from throat or respiratory infections starting early in their lives. Some had tonsillectomies at very young ages. Some of these people have reported that they had characterized immune deficiencies.

    In cases of people whose onset involved toxins, I suggest that there may be inherited genetic deficiencies in the detoxication system. These could include polymorphisms in the cytochrome P450 enzymes, or in the glutathione transferase enzymes, for examples.
    These show up fairly frequently in the Genovations Detoxigenomic Profiles that I have received from PWMEs. Although estrogens are not considered to be toxins, I have suggested in the past that women who have inherited the combination of polymorphisms in CYP1B1, COMT, and one or more of the GST enzymes are biased toward higher oxidative stress when they are catabolizing the estrogens, due to redox cycling that occurs with this combination, and I have suggested that this accounts for the higher prevalence o ME/CFS in women than in men.

    To carry this further, I now suggest that the presence of these genetic deficiencies also hinders the recovery of the people who have them.

    As many of you know, I have suggested that the GD-MCB hypothesis describes the core problem in the pathophysiology of ME/CFS. The methylation treatment, including methylfolate and high-dose B12, with some other supplements, has been shown to correct the vicious circle described by this hypothesis. However, most people who have pursued this treatment for times long enough to restore their methylation cycle, glutathione and folates, as shown by lab testing, though they report significant improvement, are still not completely recovered. I have suggested that this is due to the continuing presence of infections or toxins that were part of the etiology that caused their particular onsets, or that accumulated during the period of the illness.

    What I’m suggesting now is that a factor that allows these infections or toxins to remain, and not be eliminated by the restored immune system or the detoxication system, respectively, is that the genetic deficiencies in these systems that facilitated the onset of ME/CFS in these people are of course still present, and they are preventing full recovery by continuing to interfere with the operation of the immune system or the detoxication system.

    If this is true, then it makes sense that the immune system and/or the detoxication system will need additional help to eliminate these infections or toxins. Of course, in the case of infections, it’s also true that many pathogens have the innate capability to hide from the immune system or to frustrate its efforts, even if the immune system does not have deficiencies, and that could also be a factor in preventing the elimination of their infections.

    I’m not sure that these thoughts assist a lot in improving treatment, but perhaps they will help in understanding what’s going on. I would appreciate your thoughts on this.

    Best regards,

  2. neoplus1

    neoplus1 Member

    My symptoms began after a flu like infection, although the onset was actually delayed for a few months and slowly got worse over time rather than a sudden onset scenario.

    It would seem treatment needs to center around 3 key parts; Methylation, Mitochondrial, and Immune/Detox pathways. Many people do very well on a Methylation Protocol and many do well on a Mitochondrial Protocol. Others have used Immune modulating substances. As far as the immune component is concerned some ideas would be to actually use antiinflammatory substances since some aspects of immunity seem to be upregulated which could be what causes the immune deficiency. The immune system may become essentially "worn out."

    One example of an immune modulating substance would be probiotics and prebiotics. Some individuals have done very well with just those as a treatment although usually extremely high doses in the hundreds of billlions in some cases are used. Another example would be curcumin which also has some antifungal/antiviral/antiparasitic properties in addition to its potent NF-Kappa inhibition.

    I'm just bouncing ideas here and there. Perhaps a few methylation supplements, a few mitochondrial supplements, and a few immune modulating supplements combined could do the trick. I believe Ian's treatment for him and his family is somewhat like that and they seem to be doing better and better. I guess we'll see.
  3. IanH

    IanH Active Member

    One of the problems we face in elucidating ME is that the various treatments and "tests" eg. of viral titre, enterobacterial titre, immune system imbalance such as elevated TNF or IL-X, mitochondrial dysfunction, glutathione depletion etc. do not necessarily indicate the cause or even the "trigger" initiating the disease.

    The classic error of thinking FM is psychological because antidepressants reduce the pain has done a lot to foster mis-belief.

    I know of several people who believed their illness began with a viral infection but on close interview it appears they had ME symptoms some months before the viral infection. Just because a virus such HHV6 is elevated does not mean it caused ME, as research has shown. The raised level of HHV6, or whatever would cause problems in the immune system and in turn with the mitochondrial function (IFNb has been shown to interfere with mitochondrial function if it hangs around).

    Similarly I know of several people with MCS who believe their MCS began after exposure to a particular toxin but on reflection they were experiencing symptoms before the accused substance but the symptoms got markedly worse after the exposure.

    This is why I was against the last InvestInME theme for drug trials because it is premature. Not that we should not trial drugs for symptom relief.

    Marker identification remains paramount in research so that better quality research can occur by separating people into clusters, not according to symptoms but according to biochemistry and physiology.

    This does not attract pharmaceutical company funding so we are left with governmental support and private support for basic research and patient resolve to get justice in scientific attention.
    In fact I believe that attempts to focus on particular drugs such as rituximab can shift attention away from the needed research.[This Message was Edited on 08/13/2012]
  4. neoplus1

    neoplus1 Member

    When people test positive for various infections we have a little tendancy to jump to the conclusion that said infection is causing the illness. Even though an antimicrobial may improve someone or even put them in remission doesn't mean there is an infection. Antiparasitics, antivirals, antibiotics, and antifungals all seem to have some kind of immune modulating effect. The improvement could be because of that.

    In retrospect I think it can be very difficult to pinpoint what triggered the illness. Even in my case, I could be completely wrong thinking an infection triggered it. It may be very possible that these infections are picked up after the fact and are just making the disease worse.

    I still think that medications like rituximab should be tested though. It would be nice for many of us for there to be an approved drug that can work. Especially a drug like this because it is not something like an antidepressant. However, biological markers of disease would be invaluable. Some time ago there was a study looking at spinal fluid of patients with ME/CFS and they had distinct abnormalities compared to controls and people labeled with post lyme disease syndrome. This is huge because that can be translated to blood testing as well as figure out what the abnormalities mean.
  5. mbofov

    mbofov Active Member

    Your hypothesis makes a lot of sense. It's too bad we can't have all the necessary genetic testing to really get to the bottom of things to see if it plays out. I'm assuming this kind of testing would not be covered by Medicare?

    One thing puzzles me - I have 9 siblings (10 of us in all), and I'm the only one with CFS. Everyone else is quite healthy, except for a brother who has RSD (reflex sympathetic distrophy). So if there were a genetic component to CFS/ME, it seems to me that at least one or even possibly two would have similar symptoms to me, but they don't.

    We do have a strong family history of glaucoma. My dad had it all his life, and in just the last 3 years, 3 of my siblings (we're all in our 50's and 60's now!) now test positive for glaucoma.

    Anyways, I would not be at all surprised if further research bears out your theories - thanks for all your work on our puzzling illnesses!

  6. Mikie

    Mikie Moderator

    In my own case, I know exactly what triggered my CFIDS/ME. It was a mycoplasma infection but I don't know the exact strain. According to info provided by Dr. Garth Nicolson, my symptoms were consistent with the strain which had been bioengineered to make it weaponized and patented by a doc with affiliations to the DOD. My FMS was triggered full blown by an auto accident. Then, along came Sjogren's Syndrome just as I had gotten myself to a decent level of healing.

    I have never believed our illnesses are "caused" by any infection, trauma, stress or exposure to toxins. There appears to me to be genetic factors which do not allow us to recover from these things. An inflammatory reaction to these events seems to be fairly common. Is there a genetic overreaction by our immune systems to produce the inflammatory response which never stops even when the triggering event has been addressed? Of course, in the example of infections, you are right; many of them go chronic and stealth in the system, hiding out from the immune system. Some, like mycoplasmas and Lyme can change form and deposit cysts in bodily tissue, only to have them reactivate if one has another event.

    My Mom had FMS, both my daughters have it and one of them also has Lyme Disease. Several cousins on Mom's side have had strange immune/autoimmune illnesses which the docs have not been able to pin down. Both my daughters have interstitial cystitis and I have traces of it. From what Mom and her side of the family have told me, it sounds as though my Grandmother had FMS.

    You know of my success, so far, on the peptide injections. I don't call it a "cure." I call it having my symptoms "gone." In the case of Lyme, the researchers, who are doing studies for a peptide serum, have identified the genetic cause of the body's producing the inflammatory response. I guess what I don't understand is how these peptides can train the body to produce the proper peptide sequences even with genetic deficiencies. Can the proper peptides correct the deficiencies or do they cause the body to "bypass" the deficiency? Over the last 30 yrs. in Europe, these injections have had a better than 90 percent permanent success rate in those that are helped by them initially.

    Hope we get some more posts on this thread. It's excellent food for thought. Thanks for initiating it.

    Love, Mikie
  7. IanH

    IanH Active Member

    So what do we think of the recent paper:

  8. IanH

    IanH Active Member

    It is very hard to know when polymorphisms or when genetic damage are causing a pathology. In autism two significant risk factors are:
    low levels of maternal vitamin D
    maternal infection pre-partum which raises inflammatory cytokines.

    Both of these factors cause abnormal/subnormal neural development. Vitamin D upregulates glutathione and vitamin D deficiency, <20ng/ml causes serious depletion of glutathione, which is critical for neural development). As we know, there is a strong link between ME and autism. My daughter had ME during the birth of her second child and he has a mild ASD (impaired social communication, selective mutism and extreme intelligence in limited areas).

    What if the same maternal pre-conditions made pwme prone from the start?
    I accept that some SNPs will play a role but I doubt that SNPs are a straight forward risk factor. I suspect they play a role in the variation of the illness.
    [This Message was Edited on 08/13/2012]
  9. neoplus1

    neoplus1 Member

    But frankly I don't feel that we are just simply products of our genetic makeup. Genetic studies have frequently shown that although there are genes associated with specific diseases, many times it is just that, an association. Diet and lifestyle have been shown repeated to affect genetic expression, paticularly which genes are turned on or off at any given time.

    However, I do think confirming a link between polymorphisms of genes that dictate methylation is important to perhaps alter the protocol for certain individuals as well as decide if the protocol is even useful in their particular case. I do believe ME/CFS is a group of diseases that have similar causes and dysfunctions, but the treatment will vary depending on what subgroup you fall into. My hope is that ME/CFS will change the way medicine looks at diseases and possibly teach us a lot about other illnesses.
  10. Mikie

    Mikie Moderator

    Cancer researchers are trying to find treatments tailored to each patient's type of cancer and other factors. Someday, chemo will be looked on as barbaric.

    I think that each person who becomes ill gets caught up in a "perfect storm" of factors which make him or her sick. Very interesting studies have been done on identical twins who have identical DNA at birth. They are checked for genetic variations at intervals in their lives. The older they get, the greater the genetic changes. The old chicken 'n egg question remains, which comes first, genetic predisposition or the illness which changes us genetically. Once we are genetically changed, does it predispose our children for these illnesses. I know there is likely a genetic factor but that alone doesn't explain everything when it comes to who gets sick and who doesn't.

    Many of us have recovered from onslaughts to our immune systems only to succomb when just one more event occurs. It's kinda like the straw which breaks the camel's back. The more we learn, the more questions we have. Still, I think these questions will eventually lead to some answers.

    Rich, have you been able to find out anything about the peptide treatments? I know you were going to try. I wish I better understood this stuff but I am not a trained professional. That is why I'm so grateful to you for all you've done for us. Thanks.

    Love, Mikie
  11. richvank

    richvank New Member

    Hi, Mikie.

    No, I haven't. I don't know where to look, since it seems to be proprietary. If you know of any references or patents that discuss this type of treatment, I would be interested in reading them.

    Best regards,

  12. Mikie

    Mikie Moderator

    I've also run into a brick wall because the specifics are kept secret. The info I got from the docs was good as far as it went but it was very simplistic. Of course, that's about all I'm capable of understanding. I'll ask my doc about the genetic stuff and how the injections get around that.

    BTW, reading a good book, "In The Name of Science." There's more to the title but it delves into things like genetic issues. On my Kindle, with enlarged print, it's about 2,500 pages. I'm about half-way through. I'm reading about how our human DNA has incorporated contaminants and pathogens from the media in which vaccines are grown. Some of these changes to our DNA are thought to allow pathogens to lie latent only to activate decades later in life. This may explain the huge increases in some illnesses. Scary stuff!

    Thanks for your interest.

    Love, Mikie