ABSTRACT
We have established a new chimeric human-mouse model of myasthenia gravis in severe combined immunodeficiency mice, using human peripheral blood lymphocytes that survive in the mouse and produce specific antibodies that mediate pathological changes typical of human myasthenia gravis. Mice given peripheral blood lymphocytes from both anti-acetylcholine receptor (AChR) antibody-positive and -negative patients with myasthenia gravis showed circulating anti-acetylcholine receptor antibodies, deposition of human IgG at muscle end-plates, and simplification of the postsynaptic membrane, findings characteristic of human myasthenia gravis. Mice given human peripheral blood lymphocytes from healthy donors and simultaneously immunized with Torpedo acetylcholine receptor showed the same changes. This chimeric model, utilizing human cells to reproduce the immunopathological findings of human myasthenia gravis in a nonhuman environment, offers new opportunities to study immune regulation in autoimmunity.
Subject(s)
Disease Models, Animal , Mice, SCID/immunology , Myasthenia Gravis/immunology , Adult , Animals , Female , Humans , Immunoglobulins/biosynthesis , In Situ Hybridization, Fluorescence , Lymphocyte Transfusion , Male , Mice , Motor Endplate/immunology , Receptors, Cholinergic/immunologyABSTRACT
Treatment of Lewis rats with the beta 2-adrenergic agonist terbutaline suppressed clinical symptoms of acute passive transfer EAMG induced with monoclonal anti-acetylcholine receptor antibody and accelerated clinical recovery in affected animals. Electrophysiological studies showed that the amplitude of the first compound muscle action potential was significantly larger in terbutaline-treated rats as compared to controls. In both groups, a comparable number of inflammatory cells at the muscle endplates was seen.
Subject(s)
Immunosuppressive Agents/pharmacology , Myasthenia Gravis/prevention & control , Terbutaline/pharmacology , Acute Disease , Animals , Antibodies, Monoclonal/pharmacology , Electromyography , Female , Immunization, Passive , Motor Endplate/immunology , Motor Endplate/pathology , Myasthenia Gravis/immunology , Myasthenia Gravis/pathology , Rats , Rats, Inbred LewABSTRACT
The purpose of this study was to determine if antibodies from patients with myasthenia gravis (MG) react in a biologically relevant manner with membrane bound Torpedo californica acetylcholine receptor (AChR). Antibody-mediated complement activation was measured in plasma from 15 patients with MG and 9 controls following incubation with Torpedo AChR-rich membrane vesicles (AChR liposomes). Significantly more (p less than 0.001) complement activation occurred in the patient samples compared with the controls. Torpedo AChR liposomes are well characterized and have been widely used to study the structure and function of AChR. These results suggest that Torpedo AChR liposomes may also be used in immunologic studies with autoantibodies from patients with MG.
