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,
Rich
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,
Rich
