Increased expression of rapsyn in muscles prevents acetylcholine receptor loss in experimental autoimmune myasthenia gravis.

Myasthenia gravis is usually caused by autoantibodies to the acetylcholine receptor (AChR). The AChR is clustered and anchored in the postsynaptic membrane of the neuromuscular junction (NMJ) by a cytoplasmic protein called rapsyn. We previously showed that resistance to experimental autoimmune myasthenia gravis (EAMG) in aged rats correlates with increased rapsyn concentration at the NMJ.

Experimental autoimmune myasthenia gravis in mice expressing human immunoglobulin loci.

Antibodies (Abs) specifically directed against the muscular acetylcholine receptor (AChR) mediate the pathogenesis of myasthenia gravis (MG). The animal model experimental autoimmune MG (EAMG) can be induced by passive transfer or by active immunization of anti-AChR Abs. We report a new EAMG mouse model that generates human anti-AChR Abs upon immunization with Torpedo AChR (tAChR).

Pharmacokinetic-pharmacodynamic modeling of rocuronium in case of a decreased number of acetylcholine receptors: a study in myasthenic pigs.

Background: In myasthenic patients, the sensitivity for nondepolarizing relaxants is increased and the time course of effect is prolonged due to a reduced number of functional acetylcholine receptors at the neuromuscular junction. The authors investigated both the performance of the link model proposed by Sheiner and a pharmacodynamic-pharmacokinetic model taking into account the number of unbound acetylcholine receptors in myasthenic pigs.

Methods: After obtaining the approval of the Animal Experiments Committee of their institution, the authors studied eight myasthenic pigs and eight control pigs.

Construction and characterization of a single-chain antibody fragment derived from thymus of a patient with myasthenia gravis.

Pathogenic anti-acetylcholine receptor (AChR) antibodies in myasthenia gravis (MG) and the corresponding animal model, experimental autoimmune myasthenia gravis (EAMG), principally recognize the main immunogenic region (MIR) of the AChR. Bivalent anti-MIR antibodies binding to the alpha-subunits of AChR result in AChR loss by antigenic modulation and complement activation. Monovalent Fab and single-chain variable fragments (scFv) of pathogenic anti-AChR antibodies can interfere with AChR binding of the pathogenic antibodies.