PMID- 29339325
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20210109
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 373
DP  - 2018 Mar 1
TI  - Induction of Anti-agrin Antibodies Causes Myasthenia Gravis in Mice.
PG  - 113-121
LID - S0306-4522(18)30031-9 [pii]
LID - 10.1016/j.neuroscience.2018.01.015 [doi]
AB  - Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction 
      (NMJ). Most cases of MG are caused by autoantibodies against the acetylcholine 
      receptor (AChR), muscle-specific kinase (MuSK) and low-density lipoprotein 
      receptor-related protein 4 (LRP4). Recent studies have identified anti-agrin 
      antibodies in MG patients lacking these three antibodies (i.e., triple negative 
      MG). Agrin is a basal lamina protein that has two isoforms. Neural agrin 
      (N-agrin) binds to LRP4 to activate MuSK to induce AChR clusters and is thus 
      critical for NMJ formation. We demonstrate that mice immunized with N-agrin 
      showed MG-associated symptoms including muscle weakness, fragmented and distorted 
      NMJs. These effects were not observed in mice injected with muscle agrin 
      (M-agrin), an isoform that is inactive in inducing AChR clusters. Treatment with 
      anti-N-agrin, but not anti-M-agrin, antibodies reduced agrin-induced AChR 
      clusters in muscle cells. Together, these observations suggest that agrin 
      antibodies may be play a role in MG pathogenesis.
CI  - Copyright (c) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Yan, Min
AU  - Yan M
AD  - Institute of Life Science, Nanchang University, China; School of Basic Medical 
      Sciences, Nanchang University, China.
FAU - Liu, Ziyang
AU  - Liu Z
AD  - Institute of Life Science, Nanchang University, China.
FAU - Fei, Erkang
AU  - Fei E
AD  - Institute of Life Science, Nanchang University, China.
FAU - Chen, Wenbing
AU  - Chen W
AD  - Institute of Life Science, Nanchang University, China.
FAU - Lai, Xinsheng
AU  - Lai X
AD  - Institute of Life Science, Nanchang University, China.
FAU - Luo, Bin
AU  - Luo B
AD  - Institute of Life Science, Nanchang University, China.
FAU - Chen, Peng
AU  - Chen P
AD  - Institute of Life Science, Nanchang University, China.
FAU - Jing, Hongyang
AU  - Jing H
AD  - Institute of Life Science, Nanchang University, China.
FAU - Pan, Jin-Xiu
AU  - Pan JX
AD  - Department of Neurology, Medical College of Georgia, Augusta University, Augusta, 
      GA, USA; Charlie Norwood VA Medical Center, Augusta, GA, USA; Department of 
      Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, 
      OH, USA; Louis Stokes Cleveland VAMC, Cleveland, OH, USA.
FAU - Rivner, Michael H
AU  - Rivner MH
AD  - Department of Neurology, Medical College of Georgia, Augusta University, Augusta, 
      GA, USA.
FAU - Xiong, Wen-Cheng
AU  - Xiong WC
AD  - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 
      Augusta University, Augusta, GA, USA; Department of Neurology, Medical College of 
      Georgia, Augusta University, Augusta, GA, USA; Charlie Norwood VA Medical Center, 
      Augusta, GA, USA; Department of Neurosciences, School of Medicine, Case Western 
      Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland VAMC, Cleveland, 
      OH, USA.
FAU - Mei, Lin
AU  - Mei L
AD  - Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, 
      Augusta University, Augusta, GA, USA; Department of Neurology, Medical College of 
      Georgia, Augusta University, Augusta, GA, USA; Charlie Norwood VA Medical Center, 
      Augusta, GA, USA; Department of Neurosciences, School of Medicine, Case Western 
      Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland VAMC, Cleveland, 
      OH, USA. Electronic address: lin.mei@case.edu.
LA  - eng
GR  - R01 NS090083/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180113
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Agrin)
RN  - 0 (Autoantibodies)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Agrin/*immunology
MH  - Animals
MH  - Autoantibodies/*biosynthesis
MH  - Disease Models, Animal
MH  - Escherichia coli
MH  - Female
MH  - Immunization
MH  - Mice
MH  - Muscle Strength/immunology
MH  - Muscle, Skeletal/immunology/pathology
MH  - Myasthenia Gravis/*immunology/pathology
MH  - Neuromuscular Junction/immunology/pathology
MH  - Protein Isoforms/immunology
MH  - Receptors, Cholinergic/metabolism
MH  - Recombinant Proteins/immunology
PMC - PMC5942223
MID - NIHMS938826
OTO - NOTNLM
OT  - agrin
OT  - antibodies
OT  - myasthenia gravis
OT  - neuromuscular junction
EDAT- 2018/01/18 06:00
MHDA- 2018/11/27 06:00
PMCR- 2019/03/01
CRDT- 2018/01/18 06:00
PHST- 2017/10/21 00:00 [received]
PHST- 2017/12/27 00:00 [revised]
PHST- 2018/01/05 00:00 [accepted]
PHST- 2018/01/18 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/01/18 06:00 [entrez]
PHST- 2019/03/01 00:00 [pmc-release]
AID - S0306-4522(18)30031-9 [pii]
AID - 10.1016/j.neuroscience.2018.01.015 [doi]
PST - ppublish
SO  - Neuroscience. 2018 Mar 1;373:113-121. doi: 10.1016/j.neuroscience.2018.01.015. 
      Epub 2018 Jan 13.