title: Major pathogenic effects of anti-MuSK antibodies in myasthenia gravis.
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.
authors.affiliation: CNRS-UMR 8162, IPSC, Université Paris XI, Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis-Robinson, France.
authors.forename: Neli
authors.initials: N
authors.lastname: Boneva
authors.forename: Melinee
authors.initials: M
authors.lastname: Frenkian-Cuvelier
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Bidault
authors.forename: Talma
authors.initials: T
authors.lastname: Brenner
authors.forename: Sonia
authors.initials: S
authors.lastname: Berrih-Aknin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009133:Muscular Atrophy / Q000097:blood / Q000276:immunology / Q000503:physiopathology; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000378:metabolism / Q000503:physiopathology; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000187:drug effects / Q000276:immunology; D020764:cdc42 GTP-Binding Protein / Q000187:drug effects / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000187:drug effects / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; C051609:peripheral membrane protein 43K; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein