EBV targeting treatment yields clinical improvements in spms

[MStranslate]

Making no pretense as to understanding the science, I was blown away when I, in an effort to better understand the above article, researched the word "citrullination" in Wikipedia. So many of the subjects discussed at length in these forums appear in the Wikipedia article, and other connections can be drawn by inference (gout/no MS, MS/no gout; smoking and MS). Am I being overly optimistic in thinking that this research is, for lack of a better word, groundbreaking? What do the more scientifically-inclined think?

Hi grandsons4,

Pleasure to meet you. My name is Brett and I'm one of the co-founders of MStranslate - an organisation that aims to make research into MS easier to understand for people living with MS. My background is in MS research - having spent almost a decade investigating potential causes of multiple sclerosis.

Of possible interest to you, all of my research focussed on...citrullination! What is it that you would be interested in knowing more about when it comes to this topic? I'd be happy to let you know everything that I know.

Thanks,

[Leonard]

Let me give it a try.

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 earlier in the cells.
In periods of immune deficiency (foetal period, newborn period, period of dry eyes, ccsvi is a factor too causing weakened immunity just below the CNS), EBV may have settled its proteins in cells.
At that point, the person became predestined, but cells are still recognised as self and transgenic subjects may be healthy for life
Unless the cells is activated.

In the case of MS, herpes virinae may work together to weaken immunity (Peyer's Patches - bad gut, interaction T/B cells, hypoperfusion nasopharynx due to ccsvi).
VZV may have broken (selectively) the BBB which allowed EBV to anchor itself.
And the activation of transgenic cells follows when the microbiome 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, mitochondria slow down, insufficient ATP is produced in the cell, the ion pump lacks the energy to pump, sensory and motor function 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

Furthermore, I think the relation of citrullination and NO is not a direct relationship.
It might well be that EBV B cells are the necessary intermediate step, they are triggered as described, release their superoxide causing a reaction/link with the NO.

I should be happy to get your view and/or advice.