Immunoglobulin G structure and rheumatoid factor epitopes, 2019, Maibom-Thomsen

[Jonathan Edwards]

I think the idea is to repeat a previous study with one of the new more specific tracers. Again, I assume that most of this work uses MRI.

It seems like MS and ME are distinguishable i.e. since MS results in demyelination (detectable on MRI) and ME does not.

PET uses tomographic reconstruction from detection of radiation, MRI generates images from magnetic field perturbations in a different way. The advantage of PET is that you can study highly specific local chemical binding, to receptors etc, but otherwise it is a hugely problematic technique.

I would start from the position that MS and ME have nothing in common. MS involves local neurological lesions based on inflammatory demyelination. All sorts of minor abnormalities have been reported in ME but there is no good evidence for local lesions of a similar sort. Moreover, there is no clinical evidence for such local lesions. The only reason why ME and MS might be confused and require differentiating is that mild attacks of MS can sometimes produce too little in the way of specific signs to be diagnosed for certain. They may also be ignored by GPs or physicians who are not competent in neurological assessment.

 

[Jonathan Edwards]

Please excuse further questions. Once the autoantibody can bind (IgG changes shape) then I assume this promotes the inflammatory process.

Yes, if the autoantibody-IgG complex is outside the circulation in the tissues and the local macrophages carry the right receptors, which they do in joint tissue but not in many others.

It is often assumed that if an antibody binds to an antigen that will automatically generate inflammation but it is much more subtle than that. Binding to form complexes in the circulation does not cause inflammation because inflammation is a calling out of cells from the circulation to a tissue site. Binding in the circulation cannot call anything out anywhere because the signal is in the circulation. A different mechanism is set up if the complex deposits on the vessel wall, however.

The other side of the coin is that autoantibodies can cause harm by binding to antigens but without any inflammation - by blocking the actions of the antigen or stimulating a receptor abnormally. That is what happens in myasthenia or Graves' disease.

 

[FMMM1]

Yes, if the autoantibody-IgG complex is outside the circulation in the tissues and the local macrophages carry the right receptors, which they do in joint tissue but not in many others.

It is often assumed that if an antibody binds to an antigen that will automatically generate inflammation but it is much more subtle than that. Binding to form complexes in the circulation does not cause inflammation because inflammation is a calling out of cells from the circulation to a tissue site. Binding in the circulation cannot call anything out anywhere because the signal is in the circulation. A different mechanism is set up if the complex deposits on the vessel wall, however.

The other side of the coin is that autoantibodies can cause harm by binding to antigens but without any inflammation - by blocking the actions of the antigen or stimulating a receptor abnormally. That is what happens in myasthenia or Graves' disease.

Thank you very much for your replies. To me the mechanism are incredibly complex - but very interesting.