No abstract

The purpose of this project was t o investigate the clinical forms of acquired myasthenia gravis in dogs. The medical records from 25 dogs with seropositive acquired myasthenia gravis were reviewed, and the following data were recorded for each patient: signalment, history, clinical findings; results of IV edrophonium chloride administration, repetitive nerve stimulation, and presence or absence of muscle membrane staining by immunocytochemical methods; serum acetylcholine receptor antibody concentration; treatment; and outcome. Several clinical forms of acquired myasthenia gravis were identified. Nine of the 25 patients (36%) had no historical or clinical evidence of appendicular muscle weakness, and were designated as focalmyasthenics. These dogs exhibited focal weakness in one or more of the following muscle groups: facial (3 of 9). pharyngeal (3 of 9). and laryngeal (3 of 9). The remaining 16 dogs (64%) exhibited appendicular muscle weakness. Four of these 16 dogs had acute onset and rapid development of clinical signs, and were designated as acute fulminating myasthenics. The remaining 12 dogs were classified as generalized myasthenics. All 4 dogs with acute fulminating myasthenia gravis had megaesophagus, 2 had facial muscle weakness, and 1 had pharyngeal muscle weakness. Ten of the 12 dogs with generalized myascquired myasthenia gravis (MG) is an immune-medi-A ated disorder in which autoantibodies against nicotinic acetylcholine (ACh) receptors of skeletal muscle are produced, resulting in impairment of action potential transmission from nerve to muscle.'-6 The mechanisms proposed for the antibody impairment of neuromuscular transmission include accelerated endocytosis of antibody cross-linked ACh receptors, complement-mediated destruction of postsynaptic muscle cell membrane in the vicinity of the ACh receptors, decreased synthesis and membrane incorporation of new ACh receptors, and direct interference of ACh receptor function by bound antib~dy.'.~ Myasthenia gravis is well documented in dogs, and exhibits many similarities to the corresponding disorder of people. 1~3,S,7,x The "classic" clinical presentation of a dog with acquired MG is episodic, generalized muscle weakness, most obvious in the appendicular muscles, that is worsened by activity and ameliorated with rest.'.i.' Megaesophagus is a common finding in dogs with acquired MG because of the large proportion of skeletal muscle in the esophagus of dogs.'," In people, several clinical forms of acquired MG have been described, which has prompted the development of a number of classification schemes.2.4.6. Io.i2-i7 M ost of the classification schemes describe a focal ocular form (involving extraocular muscles) and a generalized form characterized by appendicular muscle weakness,6.~n. I Z M . IS. 17.1 n The latter is subdivided into mild, moderate, and severe forms.'"~'Z.14.1'~'7 The subdivision of generalized MG in human beings is based upon the presence and degree of bulbar and respiratory muscle involvement, and the rate of progression of clinica...

A breed predisposition for acquired MG in Abyssinians (and related Somalis) was observed. Clinical signs were variable and included generalized weakness, megaesophagus, and dysphagia. A cranial mediastinal mass was commonly associated with MG in cats.

The main immunogenic region (MIR) is a conformation-dependent region at the extracellular apex of ␣1 subunits of muscle nicotinic acetylcholine receptor (AChR) that is the target of half or more of the autoantibodies to muscle AChRs in human myasthenia gravis and rat experimental autoimmune myasthenia gravis. By making chimeras of human ␣1 subunits with ␣7 subunits, both MIR epitopes recognized by rat mAbs and by the patient-derived human mAb 637 to the MIR were determined to consist of two discontiguous sequences, which are adjacent only in the native conformation. The MIR, including loop ␣1 67-76 in combination with the N-terminal ␣ helix ␣1 1-14, conferred high-affinity binding for most rat mAbs to the MIR. However, an additional sequence corresponding to ␣1 15-32 was required for high-affinity binding of human mAb 637. A water soluble chimera of Aplysia acetylcholine binding protein with the same ␣1 MIR sequences substituted was recognized by a majority of human, feline, and canine myasthenia gravis sera. The presence of the ␣1 MIR sequences in ␣1/␣7 chimeras greatly promoted AChR expression and significantly altered the sensitivity to activation. This reveals a structural and functional, as well as antigenic, significance of the MIR.