Preprint A Proposed Mechanism for ME/CFS Invoking Macrophage Fc-gamma-RI and Interferon Gamma, 2025, Edwards, Cambridge and Cliff

[Utsikt]

As someone who had the same question and had to Google: independent or not influenced by existing ideas or assumptions

Literally, it means in a direction that has nothing in common with what has been indicated before - at right angles. It generates a cotangent of ZERO.

Thank you!

So it’s orthagonal in relation to previous ideas, not the data. That’s what was throwing me off.

 

[Jonathan Edwards]

So it’s orthagonal in relation to previous ideas, not the data. That’s what was throwing me off.

I think what EndME meant was that it was orthogonal in approach. Everyone else was taking the metro here or there and we were suggesting going up the Eiffel Tower.

 

[Utsikt]

I think what EndME meant was that it was orthogonal in approach. Everyone else was taking the metro here or there and we were suggesting going up the Eiffel Tower.

Makes sense, thank you again

 

[wigglethemouse]

Sorry if you have already covered my question in this thread. Can you explain why the "junk antibodies" in this hypothesis paper would not be detectable as a difference in the Andrew Grimson March 2025 antibody paper (thread link) that had a null result.

In the thread of that study linked above you had this to say.

It fits very well with the picture of ME/CFS immunology that is crystallising in my mind.
But it doesn't necessarily mean that B cells are not involved.

 

[Jonathan Edwards]

Sorry if you have already covered my question in this thread. Can you explain why the "junk antibodies" in this hypothesis paper would not be detectable as a difference in the Andrew Grimson March 2025 antibody paper (thread link) that had a null result.

What I hoped we had explained in the paper is that the antibodies we were invoking would not bind with the dissociation constants needed in conditions of a standard autoantibody test. The suggestion is that for steric reasons that we do not claim to know about, these antibodies may engage in interactions in the context of FcRI but not other FcR, complement, or the plastic surfaces of ELISA plates. Because FcRI can immobilise antibody even without antigen binding we know the thermodynamics of engagement are likely to be different. It is a speculation, and likely wrong, but it was a way to try to pull together a range of unexplained features.

 

[Jonathan Edwards]

The other thing is that these low affinity-for-junk antibodies might bind post-translational modification epitopes - like glycated or citrullinated proteins. These would not show up on any standard assays.