On the other thread on EBV targeting treatment yields clinical improvements in spms, there is a discussion on the role of EBV B cells and citrullination (foreign DNA).
http://multiple-sclerosis-research.blog ... cells.html
My view on this matter is as follows:
The EBV virus is ubiquitous.
I was told by an expert virologist that a high count of EBV immune complexes (from EBV B cells) in the general population is not at all unusual.
But a high count of EBV B cells alone is not enough to get MS.
There is something else that is needed.
Cells in the endothelium need to express themselves, that is a necessary condition.
So you need both: the EBV B cells and cells in the endothelium that are activated.
Our cells express themselves if HERV segments in the cells are activated.
A bad gut may trigger the HERV expression; a healthy microbiome silences the HERV segments.
Transgenic cells change phenotype, shed cytokines and chemokines.
This alerts the immune system.
At that point, you may get a cross-reaction of the EBV B cells with the transgenic cells if the B-cells find common epitopes.
And indeed, the EBV B cells find common epitopes because EBV may have anchored itself already in an earlier phase in the cells.
In periods of immune deficiency (foetal period, newborn period, transient immuno deficiency periods caused by Zoster/VZV is an immune suppressive virus (e.g. period of dry eyes), ccsvi/hypoperfusion is a factor too causing weakened immunity of the naso-pharynx in an area just below the CNS), EBV may have settled its proteins in permissible cells. [OPCs are such cells because they divide fast and after millions of years the virus has learned to go there]
VZV may have broken (selectively) the BBB prior to EBV infection.
At that point, the person became predisposed, but cells were still recognised as self. Transgenic subjects may be healthy for life.
Up to the point where the cells are activated.
In the case of MS, herpes virinae may work together to weaken immunity in the gut (Peyer's Patches, micro-biome, interaction T/B cells).
http://www.cnbc.com/2016/12/01/parkinso ... teria.html
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https://multiplesclerosisnewstoday.com/ ... -sclerosis ]]
http://apps.elsevier.es/watermark/ctl_s ... f001_2.pdf
And the activation of transgenic cells follows when the microbiome gets distorted and no longer silences the HERV.
When the cell is activated and changes phenotype, the specific immune response against the EBV infectious agent (the EBV B cells) will now cross-react with the transgenic cells that were EBV infected (because they find common epitopes).
This is causing infiltration of active immune cells and/or the release of superoxide.
For the progressive form, membranes are affected by the peroxynitrite (which is the product of superoxide with NO), mitochondria slow down, insufficient ATP is produced in the cell, the ion pump lacks the fuel/energy to pump, sensory and motor functions fail.
And you have progressive MS.
Perhaps the citrullination has something to do with cells changing phenotype.
From a quick search I find a link between citrullination and SNPs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108877/
Myelin Basic Protein as a Novel Genetic Risk Factor in Rheumatoid Arthritis—A Genome-Wide Study Combined with Immunological Analyses
For SNPs, see also my thesis on
http://www.mshackathon.nl/wp-content/up ... ressed.pdf
Furthermore, I think the relationship of citrulline and NO is not a direct relationship.
https://en.wikipedia.org/wiki/Citrullination
It might well be that EBV B cells are the necessary intermediate step, that they are triggered as described, release their superoxide causing a reaction with the NO. Where things as cause and effect are greatly mixed up.
I should be happy to get your views and/or comments.