MG is an antibody-mediated disease that is often treated with
corticosteroids.
Antibodies to the muscle specific
tyrosine kinase (
MuSK) have been identified in a proportion of patients with
myasthenia gravis (MG) without
acetylcholine receptor (AChR)
antibodies.
MuSK-MG patients often suffer from marked facial muscle weakness, and some patients develop facial and tongue
muscle atrophy.
MuSK is a
receptor tyrosine kinase that plays an essential role during development and is thought to play a trophic role in mature muscle. It is possible, therefore, that the
muscle atrophy results from the action of the
MuSK antibodies themselves, but effects of
corticosteroids on muscle might also be involved.
Muscle atrophy in vivo is associated with upregulation of striated Muscle RING-Finger protein-1 (MURF-1), and MURF-1 is also upregulated in C2C12 myotubes exposed to the
corticosteroid,
dexamethasone (Dex). Here we investigated the effects of
MuSK antibodies or Dex on MURF-1 expression in C2C12 cultures and in mouse muscles
after treatment in vivo, using quantitative Western blotting. We also looked at expression of
neural cell adhesion molecule (
NCAM, CD56) that is upregulated after
denervation in vivo.
MuSK-MG plasma and purified
IgG from a patient with marked
muscle atrophy modestly increased MURF-1 expression in C2C12 cells in culture, and MURF-1 expression in mouse masseter (facial) muscle, but not in gastrocnemius (leg). Dex had a more marked effect on MURF-1 expression in C2C12 cells, but did not affect MURF-1 expression in either muscle. However, both in C2C12 cells and in vivo, Dex substantially reduced
NCAM expression. These results provide the first evidence that
MuSK-MG plasma can influence expression of an
atrophy-related
protein, and preliminary evidence that a facial muscle, the masseter, is more susceptible to this effect. They indicate the need for further studies on
muscle atrophy,
MuSK-MG antibodies, the effects of
steroids, and the intracellular pathways involved.