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
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