Immunoregulation in Experimental Autoimmune Myasthenia Gravis—about T Cells, Antibodies, and Endplates

Abstract

Experimental autoimmune myasthenia gravis (EAMG) can be induced in a large number of animal species by active immunization (AI) AChR, by passive transfer (PT) of anti-AChR antibodies, by autologous bone marrow transplantation and cyclosporin (BMT-Cy), or spontaneously. Depending on the model used, different immunological mechanisms are operational. In the AI model, the T cell is pivotal in directing the anti-AChR antibody production towards pathogenic, that is, cross-linking and complement-fixing antibodies. Injection of anti-AChR antibodies alone suffices to induce EAMG, excluding the role of specific cell-mediated immune responses in the effector phase of the disease. Aged animals are resistant to the induction of AI and PT EAMG. This resistance is localized at the postsynaptic membrane containing more AChR-anchoring proteins, including S-laminin and rapsyn in aged animals. In BMT-CyA EAMG, a dysregulation of the immune system in the absence of immunization is capable of inducing myasthenia. The role of these animal models in relation to pathogenesis and immunotherapy is discussed.

Increased ratio of rapsyn to ACh receptor stabilizes postsynaptic receptors at the mouse neuromuscular synapse

“…In rats, the rapsyn to AChR ratio increases with ageing (Hoedemaekers et al 1998). This might explain why aged rats are resistant to anti-AChR antibody induced receptor loss (De Baets et al 2003). During AChR cluster formation, rapsyn is thought to immobilize AChRs by tethering them to the cytoskeleton (Mohamed & Swope, 1999;Moransard et al 2003), possibly via β-dystroglycan (Cartaud et al 1998;Bartoli et al 2001).…”

Immunosuppression of experimental autoimmune myasthenia gravis by mycophenolate mofetil

“…Experimental autoimmune myasthenia gravis (EAMG) in rats induced by immunization with AChRs from the electric organ of Electrophorus electricus or Torpedo californica, is already known for decades to be a reproducible and characteristic chronic model of MG (De Baets, 2003). Indeed, the presence of antibodies directed to rat muscle AChRs in the circulation of rats with EAMG provides evidence for the existence of autoimmunity in this experimental disease model.…”

Proteasome Inhibition with Bortezomib Depletes Plasma Cells and Autoantibodies in Experimental Autoimmune Myasthenia Gravis

“…In the experimental autoimmune myasthenia gravis (EAMG) model the disease is induced by immunizing rats with the AChR from the electric organ of the electric ray Torpedo californica (19,20). A small proportion of Abs against the Torpedo AChR crossreacts with the AChR of the muscle (21).…”