Abstract
MG with anti-MuSK antibodies (MuSK+) is often characterized with muscle atrophy and excellent response to plasma exchanges. To elucidate some MuSK+ MG features, we analyzed the functional effects of anti-MuSK Abs in human TE 671 muscle cells. We found that some MuSK+ sera induced a striking inhibition of proliferation, accompanied by: 1) cell cycle arrest, 2) atrogin-1 overexpression, 3) AChR subunits, rapsyn, Rho A and cdc42 downregulation. These effects correlated to disease severity and to anti-MuSK Abs titer and vanished following PE. Altogether, these results indicate that anti-MuSK Abs could be pathogenic by contributing to the muscle atrophy in MuSK+ MG patients.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Autoantibodies / blood*
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Autoantibodies / immunology*
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Autoantibodies / pharmacology
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Cell Cycle / drug effects
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Cell Cycle / immunology
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Cell Line
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Cell Proliferation / drug effects
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Cells, Cultured
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Female
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Humans
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Male
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Middle Aged
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Muscle Proteins / drug effects
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Muscle Proteins / immunology
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Muscle Proteins / metabolism
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / physiopathology
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Muscular Atrophy / blood
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Muscular Atrophy / immunology
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Muscular Atrophy / physiopathology
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Myasthenia Gravis / blood*
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Myasthenia Gravis / immunology*
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Myasthenia Gravis / physiopathology
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Neuromuscular Junction / metabolism
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Neuromuscular Junction / physiopathology
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Receptor Protein-Tyrosine Kinases / immunology*
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Receptors, Cholinergic / immunology*
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Receptors, Nicotinic / immunology
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Receptors, Nicotinic / metabolism
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SKP Cullin F-Box Protein Ligases / drug effects
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SKP Cullin F-Box Protein Ligases / immunology
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cdc42 GTP-Binding Protein / drug effects
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cdc42 GTP-Binding Protein / metabolism
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rhoA GTP-Binding Protein / drug effects
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rhoA GTP-Binding Protein / metabolism
Substances
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Autoantibodies
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Muscle Proteins
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Receptors, Cholinergic
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Receptors, Nicotinic
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peripheral membrane protein 43K
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FBXO32 protein, human
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SKP Cullin F-Box Protein Ligases
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MUSK protein, human
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Receptor Protein-Tyrosine Kinases
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cdc42 GTP-Binding Protein
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rhoA GTP-Binding Protein