Induction of experimental myasthenia gravis in Rhesus monkeys: a model for the study of the human disease

Experimental autoimmune myasthenia gravis (EAMG) was induced in thesus monkeys using purified acetylcholine recptor (AChR) from Torpedo california. A single dose of 80 µg induced antibody formation two weeks after injection. Two subsequent doses at two-week intervals caused clinical signs (anorexia, fatigability, weight loss, ptosis and dysphagia) which initially responded to treatment with neostigmine. Histologic examination of post-mortem tissues revealed lesions characteristic of myasthenia gravis in man: musuclar atrophy, fibrous degeneration and lymphocytic infiltration. Antibodies were quantitated in the sera of three other monkeys which received only 60 µg of purified AChR. Abnormally high titers persisted for two years (60-200µg/ml versus 0-10µg/ml for controls). A monkey injected with 60µgAChR as part of reconstituted membrane vesicles had lower titers (30-50µg/ml) than those which received purified receptor. Only those monkeys with antibody titers exceeding 800 µg/ml developed overt disease. These titers were 4-100 times higher than those reported for myasthenic humans. The antibody-antigen molar ratios were higher for monkeys with disease than for asymptomatic animals. These data suggest that the diversity of antibody molecules synthesized by the sensitized monkeys determined the appearance of clinical signs, and that the cross reaction of tanti-torpedo antivodies with monkey receptor was primarily responsible for the development of EAMG

Effect of immune serum on Brugia malayi microfilaria: ultra structural observations.

The in vitro effect of immune monkey serum on microfilariae of Brugia malayi was investigated using the electron microscope. The sheaths of microfilaria incubated with immune serum were seen to be covered with electron dense precipitates. After 24 hours of incubation, majority of microfilariae incubated with immune serum exhibited degenerative changes. Comparable changes were not seen in microfilariae incubated with normal serum. The significance of these observations are discussed.