Reflections on the “intrathymic pathogenesis” of myasthenia gravis

The beneficial effects of thymectomy argue for a causal role of the thymus in myasthenia gravis (MG). The MG thymus contains acetylcholine receptor (AChR), which is expressed by myoid cells (whole AChR), and by medullary thymic epithelial cells (AChR subunits). The myoid cells are closely associated with antigen-presenting dendritic cells, helper T cells, and antibody-producing B cells in lymphoid follicles (“lymphofollicular hyperplasia”). Thus, all the cellular components required to initiate and maintain an autoimmune response to AChR are present in the MG thymus. It is unlikely that the cellular alterations in the thymus are secondary to an ongoing peripheral immune response, because they are absent in experimental autoimmune myasthenia gravis.