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Penicillamine-induced myasthenia gravis

Effects of penicillamine on acetylcholine receptor

Merritt Center, Department of Neurology (Drs. Beaver, Chang, and Penn, and Mr. Bock), and the Division of Rheumatology, Department of Internal Medicine (Dr. Jaffe), College of Physicians and Surgeons of Columbia University, New York, NY.

Autoimmune diseases, including myasthenia gravis, occur in patients treated with D-penicillamine. Because D-penicillamine might induce autoantibodies by the mechanism of antigenic alteration, we studied the reaction of D-penicillamine with purified acetylcholine receptor from Torpedo californica. We found that brief exposure to D-penicillamine resulted in its covalent attachment to two receptor subunits, alpha (40,000 daltons) and gamma (59,000 Daltons), presumably by reduction and formation of mixed disulfides. Furthermore, D-penicillamine treatment resulted in a dramatic modification of the equilibrium acetylcholine binding properties of both purified receptor and receptor-rich membrane fragments.

Address correspondence and reprint requests to Dr. Penn, Merritt Center, Department of Neurology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032.

This work was supported by grants from the Muscular Dystrophy Association and the NINCDS (Nos. NS-11766 and NS-13744) and Training Grant 1T32NS07155 [C.T.B].

Presented at the thirty-third annual meeting of the American Academy of Neurology, Toronto, Ontario, Canada, May 1981.

Accepted for publication March 30, 1982.

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