PMID- 17335909
OWN - NLM
STAT- MEDLINE
DCOM- 20070606
LR  - 20220129
IS  - 0165-5728 (Print)
IS  - 0165-5728 (Linking)
VI  - 185
IP  - 1-2
DP  - 2007 Apr
TI  - Effect of sera from AChR-antibody negative myasthenia gravis patients on AChR and 
      MuSK in cell cultures.
PG  - 136-44
AB  - A proportion of patients with myasthenia gravis (MG) do not have antibodies to 
      the acetylcholine receptor (AChR). Some of these patients have antibodies to 
      muscle specific kinase (MuSK), whereas others have neither antibody (seronegative 
      MG, SNMG). Both MuSK antibody positive MG (MuSK-MG) and SNMG are 
      antibody-mediated diseases but how they cause neuromuscular junction failure is 
      not clear. One possibility is that they reduce the clustering and expression of 
      AChRs. We looked at the effects of MuSK-MG and SNMG sera/IgG on surface AChR 
      distribution and expression, and AChR subunit and MuSK mRNA by quantitative 
      RT-PCR, in TE671 and C2C12 myotubes. In TE671 cells MuSK-MG sera reduced AChR 
      expression by about 20%, but had no effect on AChR subunit or MuSK mRNA 
      expression. In C2C12 myotubes, MuSK-MG sera caused a reduction in the number of 
      agrin-induced clusters, but the clusters became larger and there was no 
      significant effect on total surface AChR numbers or AChR subunit or MuSK mRNA. By 
      contrast, SNMG sera not only reduced AChR numbers by about 20% in TE671 cells, 
      but modestly upregulated AChR gamma subunit expression in TE671 cells and both 
      AChR gamma subunit and MuSK expression in C2C12 myotubes. Thus, although these 
      results have, disappointingly, demonstrated little effect of MuSK antibodies on 
      AChR expression, they do imply that SNMG antibodies act on AChR-associated 
      pathways.
FAU - Farrugia, Maria Elena
AU  - Farrugia ME
AD  - Neurosciences Group, Weatherall Institute of Molecular Medicine, Department of 
      Clinical Neurology, University of Oxford, UK.
FAU - Bonifati, Domenico Marco
AU  - Bonifati DM
FAU - Clover, Linda
AU  - Clover L
FAU - Cossins, Judy
AU  - Cossins J
FAU - Beeson, David
AU  - Beeson D
FAU - Vincent, Angela
AU  - Vincent A
LA  - eng
GR  - G117/490/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070301
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Receptors, Nicotinic)
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  - Cells, Cultured
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunoglobulin G/immunology
MH  - In Vitro Techniques
MH  - Mice
MH  - Myasthenia Gravis/*immunology
MH  - RNA, Messenger/analysis
MH  - Receptor Protein-Tyrosine Kinases/immunology/*metabolism
MH  - Receptors, Cholinergic/immunology/*metabolism
MH  - Receptors, Nicotinic/immunology/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2007/03/06 09:00
MHDA- 2007/06/07 09:00
CRDT- 2007/03/06 09:00
PHST- 2006/12/11 00:00 [received]
PHST- 2007/01/10 00:00 [revised]
PHST- 2007/01/17 00:00 [accepted]
PHST- 2007/03/06 09:00 [pubmed]
PHST- 2007/06/07 09:00 [medline]
PHST- 2007/03/06 09:00 [entrez]
AID - S0165-5728(07)00010-0 [pii]
AID - 10.1016/j.jneuroim.2007.01.010 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2007 Apr;185(1-2):136-44. doi: 10.1016/j.jneuroim.2007.01.010. 
      Epub 2007 Mar 1.