Immunohistochemical and enzyme histochemical contributions to the problem concerning the role of the thymus in the pathogenesis of myasthenia gravis

Normal fetal and postnatal thymuses, as well as thymuses from patients with myasthenia gravis (MG), were investigated by immunohistochemical and enzyme histochemical techniques and their morphology reviewed. Intrathymic B-cells, detected by ATPase activity, were found to be markedly increased in number in MG thymuses. They were scattered in the medulla and accumulated around the junctional and medullary vessels and Hassall's corpuscles (HCs). Large epithelial cells, singly or within HCs, were found to be unevenly distributed in the medulla of all the thymuses examined. The striated muscle-like nature of some of these cells was revealed by the presence of myoglobin in their cytoplasm. In myasthenics these cells and small developing HCs characteristically surrounded lymph follicles and were in direct contact with the expanded cap of the follicle mantle, without interposition of reticulin fibres. The close association of immune reactive foci (lymphoid follicles, junctional and medullary vessels, and HCs) with structures involved in autoimmune responses in the thymus (muscle-like and true myoid cells, HCs) strongly suggests that the autoimmune reactions against AChR (acetylcholine receptor) and other muscular components, which constitute the basic defects in myasthenia gravis, may begin in the thymus.