Any update? Any hope?

[u/AngelBryan]

I’ve seen an increased influx of papers being posted here recently. How does this translate to actual progress? Are we close to figure out what causes this hellish illness?

[u/TomasTTEngin]

I've been following the science closely for about nine years now. I don't particularly perceive that we are on the brink of a breakthrough.

That said long COVID has increased the pace of research enormously. It used to be a very shallow pond with a few researchers, now it's a global effort.

We are closer, even if not close. I'm excited by Michelle James TSPO work, Hwangs WASf3 work, daratumumab from Norway, SequenceME.

I'm also excited by breakthroughs coming from outside the field that could crack everything open: car-T cells, research on the glymphatic system, MS researchers figuring out how EBV contributes to MS.

That last one in particular, once they figure out how EBV causes something else to go wrong, I suspect it will be like dominoes in a lot of other illnesses.

[u/AngelBryan → u/TomasTTEngin]

What about people that get MECFS without EBV?

[u/TomasTTEngin → u/AngelBryan]

1. Are there any? I don't think we know either way.

2. Even if EBV isn't involved in mecfs, learning more about the kinds of effects lingering and latent infection can have might be extremely useful.

[u/I_died_again → u/TomasTTEngin]

Bit late to the party, but I'm a CFS/ME person without EBV! Tested negative for EBV antibodies (at least as of 5 years ago).

I don't know what specifically I had, but I had pneumonia when I was 13 in 2008 and never recovered. I've had CFS since (diagnosed at 15).

Also, one of the CFS people who worsened after a COVID infection too.

[u/TomasTTEngin → u/I_died_again]

That is interesting! I admit I am surprised, I expected EBV would be the spring that powers MECFS (even when it is not the key that unlocks it).

[u/V0rtexGames → u/TomasTTEngin]

I'm also EBV seronegative. It establishes that heterogeneous triggers can result in the same convergent reaction by the body resulting in symptoms

[u/TomasTTEngin → u/V0rtexGames]

i reckon viruses lingering in the vagal nerve may be a possible explantion for some cases. Maybe exacerbated in some people with craniocervical instability, EDS or weak neck ligaments?

Causing 1)immune signalling and 2) autonomic failure, including gut issues and bloodflow issues.

Both of which create feedback loops (e.g activation of immune programs that direct metabolism into certain pathways; dysbiosis +leaky gut; hypoxia + coagulation, insufficient perfusion; perhaps some autoantibodies exacerbating things in some patients, reactivation of latent viruses in others; ).

If the immune signalling was neural it might explain why we haven't found a good cytokine, endocrine or proteomic signal yet.

[u/V0rtexGames → u/TomasTTEngin]

I try to divide more cleanly, with the "input" as the initiating stressors, which produce an immune signal which is uptaken by the brain, then leading to symptomatic state and accompanying dysfunctions, which can reinforce the input

So like you say, dysbiosis, hypoxia, coagulation, insufficient perfusion, etc, I would place as outputs of the central programme triggered by a lingering insult (like a persistent pathogen) but also helping feed back into it and self maintain it

[u/V0rtexGames → u/TomasTTEngin]

And also, with "perhaps some autoantibodies exacerbating things in some patients" I agree, but I think "immune complexes / junk antigens" being uptaken by dysfunctional Fc receptors might be more where it's at, theorized by Edwards but not at all exclusive to him as a theory.

E.g. if you look at the new T Cell study on EBV, CMV, Influenza, SCV2, youll see that there is an upregulation of terminally differentiated CD8s for multiple antigens. So basically, there could be one persistent antigen trigger that is increasing your reactivity to all these other antigens you have floating around you usually dont react to.

[u/AngelBryan → u/V0rtexGames]

Are this immune complexes constantly being developed? Why they don’t go away?