The possibility of autoimmunity or auto-reactivity in ME/CFS

[FMMM1]

Lets remember there are several research groups looking at T-cells in ME. I hope they find some interesting clues.....
* Jackson Group
* Anna Selin via Ramsay award
* Mark Davis
* UK ME Biobank / LSHTM (published)
* Chris Ponting

Here is an excerpt from NIH Reporter on the work Mark Davis's team is doing in ME/CFS that relates to this thread.

Source : https://projectreporter.nih.gov/pro...dvalue=&ddsub=&cr=2&csb=default&cs=ASC&pball=

As an aside, Mark Davis has a new 2020 award to look at how B and T-cells change with COVID infection in a large cohort. He has been studying influenza for a long time (Reporter shows 17+ years) but I imagine COVID has given him access to many more patients to study what happens to the immune system with infection.

Source : https://projectreporter.nih.gov/pro...dvalue=&ddsub=&cr=5&csb=default&cs=ASC&MMOpt=
(If you click on his name in this link it will show all his active projects - note, his ME one has Ron Davis as PI).

This would place Mark Davis and colleagues in a great position to study what happens to B and T cells during long COVID.

Thanks - Googled and I assume this is Chris Ponting's T-cell project - correct? https://www.actionforme.org.uk/rese...arch/research-we-fund/comparing-immune-cells/

 

[wigglethemouse]

Thanks - Googled and I assume this is Chris Ponting's T-cell project - correct? https://www.actionforme.org.uk/rese...arch/research-we-fund/comparing-immune-cells/

Yes. More info and video from CMRC 2020 in this post.
https://www.s4me.info/threads/chris-pontings-project-to-replicate-mark-davis’s-remarkable-findings-of-immune-activation-in-me-cfs-s-mcgrath-blog.4391/#post-257035

Rereading the post, they were expecting first results at the end of 2020 although the pandemic is likely to have delayed this.

 

[Snow Leopard]

How about that for an imaginative answer?

I'm just glad we managed to coax a speculative hypothesis out of you!

 

[Sly Saint]

Merged thread

FROM IACFS/ME 2021

Emerging evidence suggests that autoimmunity plays a role in postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that targeting autoantibodies could be a promising treatment approach.


Dr. Carmen Scheibenbogen

The same may also apply to many cases of “long COVID,” in which many of the symptoms overlap with those of ME/CFS, Carmen Scheibenbogen, MD, professor of clinical immunology and director of the Institute for Medical Immunology, Charité University Medicine, Berlin, said during the annual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Several groups, including Dr. Scheibenbogen’s, have reported finding autoantibodies against neurotransmitter receptor antigens in people with ME/CFS. And, in a paper published in the Journal of Clinical Medicine the day that Dr. Scheibenbogen spoke at the meeting, her team reported significant correlations between autoantibodies to vasoregulative G-protein–coupled receptors and symptom severity, autonomic dysfunction, and disability among 116 patients with infection-triggered ME/CFS who were diagnosed using the symptom-based 2003 Canadian consensus criteria.

full article here
https://www.mdedge.com/rheumatology...issue-diseases/emerging-data-point-underlying

eta: to view second page you might need to register(?)

 

[Hutan]

I'm coming from a thread that is even more enthusiastic about the possibility that Long Covid is an autoimmune disease, (i.e. characterised by the presence of autoantibodies), than Dr Scheibenbogen is in the 2021 report above:
Autoimmunity is a hallmark of post-COVID syndrome, 2022, Rojas et al

So, Rojas et al found that the majority of the Long Covid patients did have autoantibodies, but of the 100 autoantibodies or so tested for, no particular autoantibody stood out as being common. The authors did not report what percentages of healthy controls also had elevated levels of one or more autoantibodies.

So, I've come here to continue thinking about whether everyone, and certainly everyone who recently had an infection, has elevated levels of some autoantibodies. i.e. having some autoantibodies is perfectly normal. On the Rojas et al thread, I quoted a 2016 paper that suggested that some autoantibodies are helpful. It was suggested that they have a function in regulating an immune response, among other things.

There's this 2021 Russian paper that proposes an idea that is interesting:
Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

Accepting autoantibodies as a kind of bioregulator, not only the upper, but also the lower borders of their normal range should be determined; not only their excess, but also a lack of them or "autoimmunodeficiency" could be the reason for disorders.

That is, not only are some autoantibodies not harmful, but a lack them and the regulatory functions they perform might even cause problems.

 

[Jonathan Edwards]

having some autoantibodies is perfectly normal

Yes, this is basic medical student immunology.

 

[Jonathan Edwards]

There's this 2021 Russian paper that proposes an idea that is interesting:
Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

That looks garbage to me.

I worked out that the way to produce remission in RA was to target B cell clones rather than T cells despite the mockery of the immunology community and proved right. I made that decision because I had reached an understanding of how autoantibody production occurs. No fancy theories about autoantibodies being useful are needed, just the cell biology finally cracked by Michael Neuberger in the 1990s and the concept that antibody species production is random and that selecting useful species is inevitably subject to some 'software bugs' because of the way the system signals.

 

[bobbler]

CD8 T cells would be likely to be involved because they are involved in antibody-independent immune responses. CD4 T cells might very likely also be implicated but in the disease examples we have, such as psoriasis and ask spend, nobody really knows which cells are the primary problem.



T cell cytokines probably operate almost entirely locally over distances of a few microns at most -pretty much with cell contact. Circulating cytokines are probably mostly derived from macrophages and other stroll cells. In psoriasis there isn't necessarily much to find other than the local rash.



Cyclophosphamide does not deal with T cells at tolerable doses and can actually promote T cell activity, possibly by selective effects on suppressor cells. Campath 1H might well deal with the problem and I have encouraged people to try Campath in conditions like any spondylitis and psoriatic arthropathy. Unfortunately doctors are very frightened of using Campath because of the long term T cell depletion it produces. If we want to deplete T cells that seems misguided but I have never been in a position to try it myself.

The argument for trying Campth in ME is I think marginal but not to be dismissed. Before doing so it would be useful to know if anyone who has had Campath for other reasons also had ME and noticed changes.



T cells belong to at least four separate trafficking compartments - gut, skin, mucosal and everything else. So we have four T cell arthropathies - Crohn's, psoriatic, Reiter's and ankylosing spondylitis. I think it quite plausible that there is in fact yet another T cell compartment - that does not go out into any of the peripheral tissues but remains confined to lymphoid tissue. B cells remain confined to lymphoid tissue in normal immune responses. For all the functional variants of T cells there are usually 'null' groups. So there might be a 'null-trafficking' group. The interesting implication would be that persistent activation of these cells would not produce any visible local pathology but might still produce systemic symptoms due to signalling mechanisms. These might not be systemic cytokine release but might involve neural signals or other hormonal signals.

[/QUOTE]

From my experience this is starting to sound spookily close