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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.

Original publication

DOI

10.1016/j.jneuroim.2007.01.010

Type

Journal article

Journal

J Neuroimmunol

Publication Date

04/2007

Volume

185

Pages

136 - 144

Keywords

Animals, Autoantibodies, Cells, Cultured, Fluorescent Antibody Technique, Humans, Immunoglobulin G, In Vitro Techniques, Mice, Myasthenia Gravis, RNA, Messenger, Receptor Protein-Tyrosine Kinases, Receptors, Cholinergic, Receptors, Nicotinic, Reverse Transcriptase Polymerase Chain Reaction