The 'writing on the wall' hypothesis

To be clear, ECM covers collagen and elastin and everything else supporting the cell.
The signalling molecules are not on the EDS affected fibres.

And anyway, the abnormalities in EDS do not change throughout life. ME/CFS would not be due to an abnormality of ECM itself but some change in the way signals are put on to the ECM. I think that would be the implication of the paper recently posted too - that the immune system signals via the ECM through the TGF beta binding protein mechanism - which we have known about for at least thirty years.

The genetic disorder of this process is well known - ankylosing spondylitis, which is largely genetically determined and develops at about the same age predictably in all cases. The B27 gene somehow makes cells sensitive to immune signals, probably provided by CD8 T cells, which we know to be highly TGF beta sensitive and we know to recognise B27 (MHC Class I). The disease appears in exactly the same distribution as Marfan syndrome - in precisely the same 5 tissue zones.

 

Thank you, very interesting. I think what the new paper might imply is that some people with phenotypes that might resemble (or are unknown types of) EDS and are at least in part caused by some disarray in the ECM, are potentially more likely than others to trigger (via damage to parts of the ECM and or infection) immune mechanisms (presented in the paper) that might or might not lead to ME/CFS. I only read the abstract unfortunately so probably overreaching.

I don't have AS, but I am positive for the mutation, interestingly enough.

 

B27 isn't a mutation as such. It is just one of many forms of HLA-B. It probably exists because it seems to be better at protecting people against certain viruses including against clinical AIDS.

 

Interesting, at least in German both variant and mutation are used, it literally says "Mutation" on my genetic diagnostic/results, maybe they made a mistake.

 

The difference is to some extent semantic but mutation implies a variation from a standard form of the gene. There are no standard forms for MHC Class I and II genes - they exist in a wide range of variations or allelotypes, all as normal or standard as each other. Even variant tends to imply different from the norm.

I suspect diagnostic test results just use a standard term for the sake of simplicity even when it does not apply.