Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation

DB Drachman, CW Angus, RN Adams… - … England Journal of …, 1978 - Mass Medical Soc
DB Drachman, CW Angus, RN Adams, JD Michelson, GJ Hoffman
New England Journal of Medicine, 1978Mass Medical Soc
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 …
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)
The New England Journal Of Medicine