Myasthenic Antibodies Cross-Link Acetylcholine Receptors to Accelerate Degradation

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Abstract
The decrease of acetylcholine receptors at neuromuscular junctions of myasthenic patients has been attributed to an antibody-mediated autoimmune process that accelerates receptor degradation. We studied the mechanism of this process in skeletal-muscle cultures, using intact antibodies and antibody fragments. Addition of myasthenic IgG or its divalent fragment, F(ab′)2, to cultures accelerated the rate of acetylcholine-receptor degradation threefold. By contrast, the monovalent fragment, Fab, from myasthenic serum had no effect on degradation, although it bound to acetylcholine receptors. Addition of a second, "piggyback" antibody to cross-link the Fab:receptor complexes resulted in a threefold increase of the degradation rate. Similarly, when acetylcholine receptors with bound α-bungarotoxin were cross-linked by the addition of specific antibody against α-bungarotoxin, the degradation rate increased approximately threefold. The effect of myasthenic patients' antibodies in accelerating degradation of acetylcholine receptors is attributed to their ability to cross-link the receptors. (N Engl J Med 298:1116–1122, 1978)