PMID- 27408701
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160713
LR  - 20220330
IS  - 2046-1402 (Print)
IS  - 2046-1402 (Electronic)
IS  - 2046-1402 (Linking)
VI  - 5
DP  - 2016
TI  - Pathogenesis of myasthenia gravis: update on disease types, models, and 
      mechanisms.
LID - F1000 Faculty Rev-1513 [pii]
LID - 10.12688/f1000research.8206.1 [doi]
AB  - Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) 
      caused by antibodies that attack components of the postsynaptic membrane, impair 
      neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. 
      This can be generalised or localised to certain muscle groups, and involvement of 
      the bulbar and respiratory muscles can be life threatening. The pathogenesis of 
      myasthenia gravis depends upon the target and isotype of the autoantibodies. Most 
      cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the 
      acetylcholine receptor (AChR). They produce complement-mediated damage and 
      increase the rate of AChR turnover, both mechanisms causing loss of AChR from the 
      postsynaptic membrane. The thymus gland is involved in many patients, and there 
      are experimental and genetic approaches to understand the failure of immune 
      tolerance to the AChR. In a proportion of those patients without AChR antibodies, 
      antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin 
      and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK 
      antibodies are predominantly IgG4 and cause disassembly of the neuromuscular 
      junction by disrupting the physiological function of MuSK in synapse maintenance 
      and adaptation. Here we discuss how knowledge of neuromuscular junction structure 
      and function has fed into understanding the mechanisms of AChR and MuSK 
      antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated 
      conditions and these observations show how much there is still to learn about 
      synaptic function and pathological mechanisms.
FAU - Phillips, William D
AU  - Phillips WD
AD  - Physiology and Bosch Institute, University of Sydney, Anderson Stuart Bldg (F13), 
      Sydney, 2006, Australia.
FAU - Vincent, Angela
AU  - Vincent A
AD  - Neurosciences Group, Nuffield Department of Clinical Neurosciences, Weatherall 
      Institute of Molecular Medicine, University of Oxford, Oxford, UK.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160627
PL  - England
TA  - F1000Res
JT  - F1000Research
JID - 101594320
PMC - PMC4926737
OTO - NOTNLM
OT  - AChR
OT  - Myasthenia gravis
OT  - immunoglobulin
OT  - neuromuscular junction
COIS- Competing interests: The University of Oxford holds a patent for MuSK antibody 
      detection, licensed in the USA to Athena Diagnostics, and Angela Vincent receives 
      a proportion of royalties. William D. Phillips has no disclosures. No competing 
      interests were disclosed.
EDAT- 2016/07/14 06:00
MHDA- 2016/07/14 06:01
PMCR- 2016/06/27
CRDT- 2016/07/14 06:00
PHST- 2016/06/21 00:00 [accepted]
PHST- 2016/07/14 06:00 [entrez]
PHST- 2016/07/14 06:00 [pubmed]
PHST- 2016/07/14 06:01 [medline]
PHST- 2016/06/27 00:00 [pmc-release]
AID - F1000 Faculty Rev-1513 [pii]
AID - 10.12688/f1000research.8206.1 [doi]
PST - epublish
SO  - F1000Res. 2016 Jun 27;5:F1000 Faculty Rev-1513. doi: 
      10.12688/f1000research.8206.1. eCollection 2016.