Drachman suggested a few mechanisms in the attached article from New England Journal of Medicine. How has the research into this issue progressed since?
Thank you for the paper but it u 20 years old in the world of rapidly changing medicine be Careful!
Main reason for thymectomy is thymoma, mostly occult. It is not indicated in elderly with late onset of MG.
WITH BEST REGARDS DR CERNY
I think the Drachman review is good. The field of autoimmunity is now so taken over by fashion that sensible analyses like thie are increasingly hard to find. We now know more about heterogeneity of antigenic target in subgroups but the story is otherwise as he paints it.
There seems little doubt that myasthenia is due to the inappropriate survival of B cell clones that encode antibody to AChR. Since there seems to be a concentration in thymus the obvious suggestion is that for some reason anti-AChR B cells can 'parasitise' the thymic environment. The reason for this which Drachman gives and which we made use of in a review in Immunology in 1999 (on my RG page is highlighted paper) would seem to be the presence of myoid cells. These cells carry at least a subcomponent of the AChR found in muscle as I understand it, although there may be differences.
The interesting thing about myoid cells is that if they are stimulated they can reorganise the thymic architecture. So we suggested that if a B cell with surface anti-AChR got into thymus it might change the survival signal environment in such a way that it could survive and proliferate. Since the antigen would continue to be present there would be no reason not to form a follicle with a germinal centre perhaps.
People often ask what might trigger the genesis of such a rogue anti-AChR B cell but of course since all B cell specificities are generated by random Ig gene shuffling there is no need to ask this. All that is needed is that such a cell is produced and it happens to survive long enough to pop in to the thymus. Drachman is sceptical of molecular mimicry and I am even more so (as is Angela VinCent).
So removing the thymus may remove the only site where anti-AChR B cells can persist. Plasma cells in bone marrow may go on producing antibodies for years so improvement might be slow. Moreover, once one clone is up and running it is of the nature of B cell co-operation that other clones will find it easier to survive and in time they may be able to take up lodging in spleen or lymph node.
Clearly in cases of thymoma the process may be facilitated by 'danger' signals in thymus as well as myoid cells.
Jonathan Edwards lo expone de una manera muy convincente.Yo añadiria ademas la importancia de que la timectomia sea radical por esternotomia .Creo que la VATS puede resultar incomplete la timectomia.
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