Effect of myasthenic patients' immunoglobulin on acetylcholine receptor turnover: selectivity of degradation process

Daniel B Drachman, C. W. Angus, R. N. Adams, I. Kao

Research output: Contribution to journalArticle

Abstract

Antibodies in the sera of patients with myasthenia gravis are believed to play an important role in the pathogenesis of the disorder. They have recently been shown to accelerate the degradation of acetylcholine receptors in cultured mammalian skeletal muscle and at intact neuromuscular junctions. To elucidate the mechanism of the antibody-accelerated degradation process, we have prepared cultures in which one set of acetylcholine receptors was exposed to myasthenic immunoglobulin while a second set of acetycholine receptors, newly incorporated after exposure to the immunoglobulin, was not. The set of acetylcholine receptors with bound myasthenic immunoglobulin was degraded at 2 to 3 times the normal rate, while the second set of acetylcholine receptors without bound immunoglobulin was degraded at the control rate. This suggests that the binding of antibody from myasthenic patients alters the acetylcholine receptors in some way that causes them to be selected for preferential degradation by the muscle cells. New synthesis and incorporation of the acetylcholine receptors into the surface membrane of cultured skeletal muscle was unaffected by exposure to myasthenic immunoglobulin.

Original languageEnglish (US)
Pages (from-to)3422-3426
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume75
Issue number7
StatePublished - 1978

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Muscle Weakness
Cholinergic Receptors
Immunoglobulins
Antibodies
Skeletal Muscle
Neuromuscular Junction
Myasthenia Gravis
Muscle Cells
Membranes
Serum

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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abstract = "Antibodies in the sera of patients with myasthenia gravis are believed to play an important role in the pathogenesis of the disorder. They have recently been shown to accelerate the degradation of acetylcholine receptors in cultured mammalian skeletal muscle and at intact neuromuscular junctions. To elucidate the mechanism of the antibody-accelerated degradation process, we have prepared cultures in which one set of acetylcholine receptors was exposed to myasthenic immunoglobulin while a second set of acetycholine receptors, newly incorporated after exposure to the immunoglobulin, was not. The set of acetylcholine receptors with bound myasthenic immunoglobulin was degraded at 2 to 3 times the normal rate, while the second set of acetylcholine receptors without bound immunoglobulin was degraded at the control rate. This suggests that the binding of antibody from myasthenic patients alters the acetylcholine receptors in some way that causes them to be selected for preferential degradation by the muscle cells. New synthesis and incorporation of the acetylcholine receptors into the surface membrane of cultured skeletal muscle was unaffected by exposure to myasthenic immunoglobulin.",
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T2 - selectivity of degradation process

AU - Drachman, Daniel B

AU - Angus, C. W.

AU - Adams, R. N.

AU - Kao, I.

PY - 1978

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AB - Antibodies in the sera of patients with myasthenia gravis are believed to play an important role in the pathogenesis of the disorder. They have recently been shown to accelerate the degradation of acetylcholine receptors in cultured mammalian skeletal muscle and at intact neuromuscular junctions. To elucidate the mechanism of the antibody-accelerated degradation process, we have prepared cultures in which one set of acetylcholine receptors was exposed to myasthenic immunoglobulin while a second set of acetycholine receptors, newly incorporated after exposure to the immunoglobulin, was not. The set of acetylcholine receptors with bound myasthenic immunoglobulin was degraded at 2 to 3 times the normal rate, while the second set of acetylcholine receptors without bound immunoglobulin was degraded at the control rate. This suggests that the binding of antibody from myasthenic patients alters the acetylcholine receptors in some way that causes them to be selected for preferential degradation by the muscle cells. New synthesis and incorporation of the acetylcholine receptors into the surface membrane of cultured skeletal muscle was unaffected by exposure to myasthenic immunoglobulin.

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