PMID- 23537506
OWN - NLM
STAT- MEDLINE
DCOM- 20140106
LR  - 20190318
IS  - 1873-0183 (Electronic)
IS  - 1568-9972 (Linking)
VI  - 12
IP  - 9
DP  - 2013 Jul
TI  - Mechanisms associated with the pathogenicity of antibodies against 
      muscle-specific kinase in myasthenia gravis.
PG  - 912-7
LID - S1568-9972(13)00031-1 [pii]
LID - 10.1016/j.autrev.2013.03.005 [doi]
AB  - The presence of autoantibodies against muscle-specific kinase (MuSK) at the 
      neuromuscular junction (NMJ) results in myasthenia gravis (MG). MuSK 
      antibody-associated MG (MuSK MG) patients often have severe symptoms, including 
      bulbar dysfunction, respiratory insufficiency and atrophy of the facial and 
      tongue muscles. MuSK antibodies in MG patients predominantly belong to the IgG4 
      subclass, and the unique properties of IgG4 antibodies are directly associated 
      with the pathogenic mechanisms of MuSK MG. Histopathological studies in animal 
      models of MuSK MG have revealed that anti-MuSK antibodies cause contraction of 
      motor terminals, significant loss of acetylcholine receptor (AChR) expression, 
      and a reduction in synaptic folds at the postsynaptic membrane in the absence of 
      complement involvement. Failure of neuromuscular transmission at pre- and 
      postsynaptic membranes of the NMJs has been observed in both patients and animal 
      models of MuSK MG. A murine model of MuSK-MG revealed the mechanisms underlying 
      cholinergic hypersensitivity after administration of acetylcholinesterase 
      inhibitors, which has also been observed in MuSK-MG patients. Further studies of 
      this model have provided evidence suggesting that 3,4-diaminopyridine may be 
      effective as a symptomatic therapy for MuSK MG.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Mori, Shuuichi
AU  - Mori S
AD  - Department of Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, 
      Tokyo 173-0015, Japan.
FAU - Shigemoto, Kazuhiro
AU  - Shigemoto K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130326
PL  - Netherlands
TA  - Autoimmun Rev
JT  - Autoimmunity reviews
JID - 101128967
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Autoantibodies/*immunology
MH  - Humans
MH  - Immunoglobulin G/*immunology
MH  - Muscle, Skeletal/metabolism/pathology/physiopathology
MH  - Myasthenia Gravis/*immunology/*pathology/therapy
MH  - Neuromuscular Junction/pathology/physiopathology
MH  - Receptor Protein-Tyrosine Kinases/immunology
MH  - Receptors, Cholinergic/immunology/metabolism
MH  - Synaptic Membranes/metabolism/pathology
EDAT- 2013/03/30 06:00
MHDA- 2014/01/07 06:00
CRDT- 2013/03/30 06:00
PHST- 2013/03/12 00:00 [accepted]
PHST- 2013/03/30 06:00 [entrez]
PHST- 2013/03/30 06:00 [pubmed]
PHST- 2014/01/07 06:00 [medline]
AID - S1568-9972(13)00031-1 [pii]
AID - 10.1016/j.autrev.2013.03.005 [doi]
PST - ppublish
SO  - Autoimmun Rev. 2013 Jul;12(9):912-7. doi: 10.1016/j.autrev.2013.03.005. Epub 2013 
      Mar 26.