PMID- 29356029
OWN - NLM
STAT- MEDLINE
DCOM- 20190311
LR  - 20190610
IS  - 1749-6632 (Electronic)
IS  - 0077-8923 (Linking)
VI  - 1413
IP  - 1
DP  - 2018 Feb
TI  - Passive transfer models of myasthenia gravis with muscle-specific kinase 
      antibodies.
PG  - 111-118
LID - 10.1111/nyas.13543 [doi]
AB  - Myasthenia gravis (MG) with antibodies to muscle-specific kinase (MuSK) is 
      characterized by fluctuating fatigable weakness. In MuSK MG, involvement of 
      bulbar muscles, neck, and shoulder and respiratory weakness are more prominent 
      than in acetylcholine receptor (AChR) MG. MuSK autoantibodies are mainly of the 
      IgG4 subclass, and as such are unable to activate complement, have low affinity 
      for Fc receptors, and are functionally monovalent. Therefore, the pathogenicity 
      of IgG4 MuSK autoantibodies was initially questioned. A broad collection of in 
      vitro active immunization and passive transfer models has been developed that 
      have shed light on the pathogenicity of MuSK autoantibodies. Passive transfer 
      studies with purified IgG4 from MuSK MG patients confirmed that IgG4 is 
      sufficient to reproduce clear clinical, electrophysiological, and histological 
      signs of myasthenia. In vitro experiments revealed that MuSK IgG4 autoantibodies 
      preferably bind the first Ig-like domain of MuSK, correlate with disease 
      severity, and interfere with the association between MuSK and low-density 
      lipoprotein receptor-related protein 4 and collagen Q. Some patients have 
      additional IgG1 MuSK autoantibodies, but their role in the disease is unclear. 
      Altogether, this provides a rationale for epitope-specific or IgG4-specific 
      treatment strategies for MuSK MG and emphasizes the importance of the development 
      of different experimental models.
CI  - (c) 2018 New York Academy of Sciences.
FAU - Verschuuren, Jan J G M
AU  - Verschuuren JJGM
AD  - Department of Neurology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Plomp, Jaap J
AU  - Plomp JJ
AD  - Department of Neurology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Burden, Steve J
AU  - Burden SJ
AD  - Kimmel Center for Biology and Medicine at the Skirball Institute, New York 
      University Medical School, New York, New York.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Kimmel Center for Biology and Medicine at the Skirball Institute, New York 
      University Medical School, New York, New York.
FAU - Fillie-Grijpma, Yvonne E
AU  - Fillie-Grijpma YE
AD  - Department of Neurology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Stienstra-van Es, Inge E
AU  - Stienstra-van Es IE
AD  - Department of Neurology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Niks, Erik H
AU  - Niks EH
AD  - Department of Neurology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Losen, Mario
AU  - Losen M
AD  - Department of Psychiatry and Neuropsychology, School for Mental Health and 
      Neuroscience, Maastricht University, Maastricht, the Netherlands.
FAU - van der Maarel, Silvere M
AU  - van der Maarel SM
AD  - Department of Neurology, Leiden University Medical Center, Leiden, the 
      Netherlands.
FAU - Huijbers, Maartje G
AU  - Huijbers MG
AD  - Department of Neurology, Leiden University Medical Center, Leiden, the 
      Netherlands.
LA  - eng
GR  - R01 NS036193/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20180121
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Autoantibodies/*immunology
MH  - Disease Models, Animal
MH  - Humans
MH  - Immunization, Passive/*methods
MH  - Immunoglobulin G/*immunology
MH  - Mice
MH  - Muscle Weakness/genetics/pathology
MH  - Myasthenia Gravis/genetics/*immunology/*pathology
MH  - Receptor Protein-Tyrosine Kinases/*immunology
MH  - Receptors, Cholinergic/*immunology
OTO - NOTNLM
OT  - animal model
OT  - autoimmune
OT  - muscle-specific kinase
OT  - myasthenia gravis
OT  - passive transfer
EDAT- 2018/01/23 06:00
MHDA- 2019/03/12 06:00
CRDT- 2018/01/23 06:00
PHST- 2017/08/22 00:00 [received]
PHST- 2017/10/02 00:00 [revised]
PHST- 2017/10/05 00:00 [accepted]
PHST- 2018/01/23 06:00 [pubmed]
PHST- 2019/03/12 06:00 [medline]
PHST- 2018/01/23 06:00 [entrez]
AID - 10.1111/nyas.13543 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2018 Feb;1413(1):111-118. doi: 10.1111/nyas.13543. Epub 2018 
      Jan 21.