D-Penicillamine-associated myasthenia gravis: immunological and electrophysiological studies

Immunological and electrophysiological features were investigated in a patient with rheumatoid arthritis who developed myasthenic symptoms after 10 months of treatment with D-penicillamine (D-pen). After an initial rise, acetylcholine receptor (AChR) antibodies gradually fell from 24.4 nmole alpha-bungarotoxin bound/liter to 1.8 nmole/liter following withdrawal of the drug, and this was associated with clinical and electrophysiological improvement. Immunoglobuline synthesis by peripheral blood lymphocytes cultured with pokeweed mitogen and D-pen was significantly increased at D-pen concentrations of 10-100 micrograms/ml in 2 patients with D-pen associated myasthenia gravis and 1 out of 3 normal individuals. Furthermore, lymphocytes from 1 myasthenic patient synthesized detectable AChR antibodies in vitro, and the amount of receptor antibody produced was increased in the presence of the drug. This effect was most marked at a concentration of 10 micrograms/ml which is thought to approximate the concentration in vivo. Our results confirm the in vivo findings of others that D-pen may have different effects on immunoglobulin production in different individuals and may also enhance the snythesis of at least 1 autoantibody, the AChR antibody.