title: Clinical and scientific aspects of muscle-specific tyrosine kinase-related myasthenia gravis.
abstract: OBJECTIVE
  Antibodies to muscle-specific tyrosine kinase (MuSK) characterize up to 5% of myasthenia gravis patients. This review focuses on the differences to clinical antiacetylcholine receptor-myasthenia gravis, and on the physiology and animal studies that elucidate the role of MuSK and help explain the clinical disease.
  
  
  RESULTS
  MuSK forms the core of a protein complex in the postsynaptic membrane at the neuromuscular junction. During development, MuSK tyrosine kinase signaling is vital for the formation and stabilization of the postsynaptic endplate; it is now clear that long-term homeostasis of mature neuromuscular junctions requires MuSK function. Patient MuSK-antibodies are largely of the IgG4 type and in cell culture block the assembly and activation of MuSK kinase. Active immunization and passive transfer mouse models show reduced postsynaptic acetylcholine receptors and disturbed synaptic alignment, diminished synaptic potentials and impaired muscle activation.MuSK myasthenia gravis patients display particular bulbar and respiratory muscle involvement, with a high rate of myasthenic crises. Plasma exchange and immunosuppression with corticosteroids and rituximab appear to be most effective in treating MuSK myasthenia gravis. In contrast, the cholinesterase inhibitors, such as pyridostigmine, appear less suitable for this form of myasthenia gravis.
  
  
  CONCLUSIONS
  MuSK myasthenia gravis has distinct clinical and pathophysiological features.
authors.affiliation: aDepartments of Molecular Medicine & Neurology, Concord Clinical School, University of Sydney bMotor Neurone Diseases Research Group, Australian School of Advanced Medicine, Macquarie University cPhysiology and Bosch Institute, University of Sydney, New South Wales, Australia.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Reddel
authors.forename: Marco
authors.initials: M
authors.lastname: Morsch
authors.forename: William D
authors.initials: WD
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D004195:Disease Models, Animal; D006801:Humans; D007165:Immunosuppression Therapy; D009157:Myasthenia Gravis / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology / Q000628:therapy*; D009469:Neuromuscular Junction / Q000503:physiopathology*; D010951:Plasma Exchange; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D020794:Receptor Protein-Tyrosine Kinases