In a nutshell which side is winning in your opinion?
I do not see these aspects as in competition. I see them as orthogonal - the rightness of one has no particular bearing on the rightness of the other.
We need to understand the neurological pathways involved. I don't see any doubt in neurological pathways being involved. Whether people are homing in on the 'right' neurons seems to me unimportant. You have to home in to test ideas. Paolo is the first to say that the point of an idea is to punish it with data. I think everyone involved recognises Chris P's caveats. Differential gene expression need not point in the right place at all. But we might be lucky .
We also need to understand how immune stimuli like infection trigger the illness, as it seems they often do. Here the question is different - around whether antibodies are important, and if so whether they need to be autoantibodies, or whether the immune shift is in T cells, T-like cells such as NK, MAIT, or even myeloid/monocyte lineage cells. There are also questions about latent viruses such as Herpes.
The weight of evidence, including the absence of any DR signal on DecodeME, is against a big role for autoantibodies but the therapeutic studies with Daratumumab remain tantalising.
And we have some suggestions that ME/CFS may arise from a 'two hit' sequence. The first hit may look like post-viral fatigue and the second, the more persistent and sometimes progressive illness with severe features. I was reminded of this by a ceiling light failing at home. Sometimes when a bulb is dodgy it trips the switchboard. Sometimes it just blows. Sometimes both happen at once. I suspect what we are trying to find may be two weak points in the global system, where the normal rules can flip into a counterproductive state - very much as Robert Phair was proposing with the itaconate shunt.
