PMID- 24632822
OWN - NLM
STAT- MEDLINE
DCOM- 20141228
LR  - 20220419
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 3
DP  - 2014
TI  - Autoantibodies to agrin in myasthenia gravis patients.
PG  - e91816
LID - 10.1371/journal.pone.0091816 [doi]
LID - e91816
AB  - To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a 
      proteoglycan released by motor neurons and is critical for neuromuscular junction 
      (NMJ) formation, we collected serum samples from 93 patients with MG with known 
      status of antibodies to acetylcholine receptor (AChR), muscle specific kinase 
      (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects 
      (healthy individuals and individuals with other diseases). Sera were assayed for 
      antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG 
      patients. None of the 25 healthy controls and none of the 55 control neurological 
      patients had agrin antibodies. Two of the four triple negative MG patients (i.e., 
      no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies 
      against agrin. In addition, agrin antibodies were detected in 5 out of 83 
      AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK 
      antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were 
      able to recognize recombinant agrin in conditioned media and in transfected 
      HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation 
      and AChR clustering in muscle cells. Together, these observations indicate that 
      agrin is another autoantigen in patients with MG and agrin autoantibodies may be 
      pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ.
FAU - Zhang, Bin
AU  - Zhang B
AD  - Department of Neuroscience and Regenerative Medicine and Department of Neurology, 
      Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United 
      States of America; Department of Physiology, Basic Medical School, Tongji Medical 
      College, Huazhong University of Science & Technology, Wuhan, Hubei Province, P. 
      R. China.
FAU - Shen, Chengyong
AU  - Shen C
AD  - Department of Neuroscience and Regenerative Medicine and Department of Neurology, 
      Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United 
      States of America; Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States of America.
FAU - Bealmear, Beverly
AU  - Bealmear B
AD  - Department of Neurology, School of Medicine, Wayne State University, Detroit, 
      Michigan, United States of America.
FAU - Ragheb, Samia
AU  - Ragheb S
AD  - Department of Neurology, School of Medicine, Wayne State University, Detroit, 
      Michigan, United States of America; Department of Biomedical Sciences, Oakland 
      University William Beaumont School of Medicine, Rochester, Michigan, United 
      States of America.
FAU - Xiong, Wen-Cheng
AU  - Xiong WC
AD  - Department of Neuroscience and Regenerative Medicine and Department of Neurology, 
      Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United 
      States of America; Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States of America.
FAU - Lewis, Richard A
AU  - Lewis RA
AD  - Department of Neurology, School of Medicine, Wayne State University, Detroit, 
      Michigan, United States of America; Department of Neurology, Cedars-Sinai Medical 
      Center, West Hollywood, California, United States of America.
FAU - Lisak, Robert P
AU  - Lisak RP
AD  - Department of Neurology, School of Medicine, Wayne State University, Detroit, 
      Michigan, United States of America; Department of Immunology and Microbiology, 
      School of Medicine, Wayne State University, Detroit, Michigan, United States of 
      America.
FAU - Mei, Lin
AU  - Mei L
AD  - Department of Neuroscience and Regenerative Medicine and Department of Neurology, 
      Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United 
      States of America; Charlie Norwood VA Medical Center, Augusta, Georgia, United 
      States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140314
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Agrin)
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
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  - Agrin/*immunology
MH  - Autoantibodies/blood/*immunology
MH  - Autoantigens/immunology
MH  - Humans
MH  - Myasthenia Gravis/*immunology/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Cholinergic/immunology/metabolism
PMC - PMC3954737
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/03/19 06:00
MHDA- 2014/12/30 06:00
PMCR- 2014/03/14
CRDT- 2014/03/18 06:00
PHST- 2014/01/23 00:00 [received]
PHST- 2014/02/02 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
PHST- 2014/03/14 00:00 [pmc-release]
AID - PONE-D-14-01782 [pii]
AID - 10.1371/journal.pone.0091816 [doi]
PST - epublish
SO  - PLoS One. 2014 Mar 14;9(3):e91816. doi: 10.1371/journal.pone.0091816. eCollection 
      2014.