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https://www.researchgate.net/profile/Wa ... munity.pdf
Pathogenesis of Multiple Sclerosis: How Much Space is Left for Autoimmunity?
Abstract
Multiple Sclerosis (MS) is generally considered an autoimmune disease, mainly because the preferred and wellstudied
animal models for the disease are autoimmune models. In human disease, however, evidence for
autoimmunity in MS has been sought for a long time with marginal results. On the other hand, two viruses, EBV and
HHV-6A, play an etio-pathogenic role and, as recently discussed, their mutual interaction might be a key element in
the pathogenesis of MS. This short review summarizes evidence that supports this view of changing the paradigm
about the etio-pathogenesis of MS from autoimmunity to viral.
more evidence against the autoimmune model
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centenarian100
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Re: more evidence against the autoimmune model
The connection to EBV and autoimmunity are not necessarily mutually exclusive. One of the theories about the pathogenesis of MS is that b cells are infected by EBV and become less regulated by CD25 regulatory t cells. Just because abnormal immune system function may be the "proximate" cause of MS does not necessarily mean that it is the "Ultimate" cause of MS. I'm using Jared Diamond's terms which are hopefully not too ambiguous. MS might be the end result of a combination of environmental factors (low vitamin D, EBV, smoking, hygeine) in the genetically susceptible host.
You can read more about the effect of EBV on B lymphocytes here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199828/
It is almost as though EBV is a "necessary but not sufficient" cause of multiple sclerosis
There is even some evidence that intracerebral EBV activation may be associated with MS relapses:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623710/
The best evidence that MS is primarily an autoimmune disease is the genetic evidence suggesting that the genes most associated with MS have to do with the immune system. Being homozygous for MHC DRB1 1501 gives an 8 fold increased risk. Also, the efficacy of immunosuppressants in relapsing multiple sclerosis calls to question the idea that MS is primarily an infectious disease. Is there any other neuroinfectious disease where bone marrow transplant leads to improvement? AIDS increases the risk of CNS infections (toxoplasmosis, histoplasmosis, cryptococcosis) but is somehow inversely related to MS even corrected for age and sex. How could this be the case if MS is primarily an infectious disease? Just food for thought.
You can read more about the effect of EBV on B lymphocytes here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199828/
It is almost as though EBV is a "necessary but not sufficient" cause of multiple sclerosis
There is even some evidence that intracerebral EBV activation may be associated with MS relapses:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623710/
The best evidence that MS is primarily an autoimmune disease is the genetic evidence suggesting that the genes most associated with MS have to do with the immune system. Being homozygous for MHC DRB1 1501 gives an 8 fold increased risk. Also, the efficacy of immunosuppressants in relapsing multiple sclerosis calls to question the idea that MS is primarily an infectious disease. Is there any other neuroinfectious disease where bone marrow transplant leads to improvement? AIDS increases the risk of CNS infections (toxoplasmosis, histoplasmosis, cryptococcosis) but is somehow inversely related to MS even corrected for age and sex. How could this be the case if MS is primarily an infectious disease? Just food for thought.
Re: more evidence against the autoimmune model
More voices against the autoimmune model:
Source:
Abstract: https://www.futuremedicine.com/doi/full ... ebo.12.277
The inflammatory demyelinating lesions that are characteristic of multiple sclerosis (MS) are traditionally seen as the result of an autoimmune attack by activated T cells that invade an otherwise normal CNS. In this view, the primary trigger for MS is inadvertent activation of a peripheral repertoire of myelin-reactive T cells.
However, decades of research have failed to uncover any myelin-specific autoimmune abnormality in the circulation of MS patients. At the same time, evidence has accumulated for the existence of local tissue disturbances in the CNS that emerge in the absence of immune infiltration, and can precede the development of a demyelinating lesion by weeks or months.
Here, we review the evidence that MS lesions are triggered by an endogenous problem within the CNS itself, rather than by any peripheral autoimmune abnormality. This altered view has obvious consequences for the way strategies to modify the disease course is looked upon in MS.
And a similar report:
Demyelination with preferential MAG loss: A complex message from MS paraffin blocks
http://www.jns-journal.com/article/S002 ... 3/fulltext
Abstract
Multiple sclerosis (MS) is generally considered to be a demyelinating autoimmune disorder. However, neuropathological examinations of MS lesions do not support this concept. Demyelination with preferential loss of myelin-associated glycoprotein (MAG) is a common finding in MS tissues and has been reported by several groups. As MAG is located in ad-axonal myelin layers and is not accessible to infiltrating immune cells, demyelination with preferred loss of MAG may be suggestive of a primary oligodendrocytopathy in MS. Moreover, it has been shown that oligodendrocytopathy may precede the infiltration of inflammatory cells at the lesion site. In this paper, we review studies of neuropathology of MS tissues that reported this type of demyelination and then we discuss three emerging explanations that are trying to interpret this mismatched observation.
Source:
Abstract: https://www.futuremedicine.com/doi/full ... ebo.12.277
The inflammatory demyelinating lesions that are characteristic of multiple sclerosis (MS) are traditionally seen as the result of an autoimmune attack by activated T cells that invade an otherwise normal CNS. In this view, the primary trigger for MS is inadvertent activation of a peripheral repertoire of myelin-reactive T cells.
However, decades of research have failed to uncover any myelin-specific autoimmune abnormality in the circulation of MS patients. At the same time, evidence has accumulated for the existence of local tissue disturbances in the CNS that emerge in the absence of immune infiltration, and can precede the development of a demyelinating lesion by weeks or months.
Here, we review the evidence that MS lesions are triggered by an endogenous problem within the CNS itself, rather than by any peripheral autoimmune abnormality. This altered view has obvious consequences for the way strategies to modify the disease course is looked upon in MS.
And a similar report:
Demyelination with preferential MAG loss: A complex message from MS paraffin blocks
http://www.jns-journal.com/article/S002 ... 3/fulltext
Abstract
Multiple sclerosis (MS) is generally considered to be a demyelinating autoimmune disorder. However, neuropathological examinations of MS lesions do not support this concept. Demyelination with preferential loss of myelin-associated glycoprotein (MAG) is a common finding in MS tissues and has been reported by several groups. As MAG is located in ad-axonal myelin layers and is not accessible to infiltrating immune cells, demyelination with preferred loss of MAG may be suggestive of a primary oligodendrocytopathy in MS. Moreover, it has been shown that oligodendrocytopathy may precede the infiltration of inflammatory cells at the lesion site. In this paper, we review studies of neuropathology of MS tissues that reported this type of demyelination and then we discuss three emerging explanations that are trying to interpret this mismatched observation.