PMID- 22158716
OWN - NLM
STAT- MEDLINE
DCOM- 20120531
LR  - 20220321
IS  - 1538-3687 (Electronic)
IS  - 0003-9942 (Linking)
VI  - 69
IP  - 4
DP  - 2012 Apr
TI  - Autoantibodies to lipoprotein-related protein 4 in patients with 
      double-seronegative myasthenia gravis.
PG  - 445-51
LID - 10.1001/archneurol.2011.2393 [doi]
AB  - OBJECTIVES: To determine whether patients with myasthenia gravis (MG) have serum 
      antibodies to lipoprotein-related protein 4 (LRP4), a newly identified receptor 
      for agrin that is essential for neuromuscular junction formation, and to 
      establish whether such antibodies contribute to MG pathogenesis. DESIGN: Serum 
      samples from patients with MG with known status of serum antibodies to the 
      acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) and serum samples 
      from control subjects (healthy individuals and individuals with other diseases) 
      were tested for antibodies to LRP4. Serum samples with such antibodies were 
      tested to determine whether they had the ability to inhibit 2 different functions 
      of LRP4 at the neuromuscular junction. SETTING: Serum samples were collected at 
      the Hellenic Pasteur Institute and Wayne State University. Samples were tested 
      for LRP4 autoantibodies at Georgia Health Sciences University. Other 
      immunoreactivities of the samples were tested at the Hellenic Pasteur Institute, 
      Athens, Greece, or processed through University Laboratories of the Detroit 
      Medical Center, Michigan. Patients  The study included 217 patients with MG, 76 
      patients with other neurologic or psychiatric diseases, and 45 healthy control 
      subjects. RESULTS: Anti-LRP4 antibodies were detected in 11 of 120 patients with 
      MG without detectable anti-AChR or anti-MuSK antibodies (double seronegative) and 
      in 1 of 36 patients without anti-AChR antibodies but with anti-MuSK antibodies, 
      but they were not detected in any of the 61 patients with anti-AChR antibodies. 
      No healthy control subjects and only 2 of the 76 control patients with neurologic 
      disease had anti-LRP4 antibodies. Serum samples from patients with MG with 
      anti-LRP4 antibodies were able to inhibit the LRP4-agrin interaction and/or alter 
      AChR clustering in muscle cells. CONCLUSIONS: Anti-LRP4 antibodies were detected 
      in the serum of approximately 9.2% of patients with double-seronegative MG. This 
      frequency is intermediate compared with 2 recent studies showing anti-LRP4 
      antibodies in 2% and 50% of patients with double-seronegative MG from different 
      geographic locations. Together, these observations indicate that LRP4 is another 
      autoantigen in patients with MG, and anti-LRP4 autoantibodies may be pathogenic 
      through different immunopathogenic processes.
FAU - Zhang, Bin
AU  - Zhang B
AD  - Department of Neurology, Institute of Molecular Medicine and Genetics, Georgia 
      Health Sciences University, 1120 15th St, Augusta, GA 30912, USA.
FAU - Tzartos, John S
AU  - Tzartos JS
FAU - Belimezi, Maria
AU  - Belimezi M
FAU - Ragheb, Samia
AU  - Ragheb S
FAU - Bealmear, Beverly
AU  - Bealmear B
FAU - Lewis, Richard A
AU  - Lewis RA
FAU - Xiong, Wen-Cheng
AU  - Xiong WC
FAU - Lisak, Robert P
AU  - Lisak RP
FAU - Tzartos, Socrates J
AU  - Tzartos SJ
FAU - Mei, Lin
AU  - Mei L
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111212
PL  - United States
TA  - Arch Neurol
JT  - Archives of neurology
JID - 0372436
RN  - 0 (Agrin)
RN  - 0 (Autoantibodies)
RN  - 0 (LDL-Receptor Related Proteins)
RN  - 0 (LRP4 protein, human)
RN  - 0 (Receptors, Cholinergic)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
CIN - Arch Neurol. 2012 Apr;69(4):434-5. PMID: 22158717
MH  - Agrin/metabolism
MH  - Autoantibodies/*blood/pharmacology
MH  - Cell Line, Transformed
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Immunoprecipitation
MH  - LDL-Receptor Related Proteins/chemistry/*immunology
MH  - Male
MH  - Multiple Sclerosis/blood/immunology
MH  - Myasthenia Gravis/*blood/*immunology
MH  - Neuromyelitis Optica/blood/immunology
MH  - Receptor Protein-Tyrosine Kinases/immunology
MH  - Receptors, Cholinergic/immunology
MH  - Schizophrenia/blood/immunology
MH  - Serotonin/*metabolism
MH  - Transfection
EDAT- 2011/12/14 06:00
MHDA- 2012/06/01 06:00
CRDT- 2011/12/14 06:00
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/06/01 06:00 [medline]
AID - archneurol.2011.2393 [pii]
AID - 10.1001/archneurol.2011.2393 [doi]
PST - ppublish
SO  - Arch Neurol. 2012 Apr;69(4):445-51. doi: 10.1001/archneurol.2011.2393. Epub 2011 
      Dec 12.