The influence of age on the induction of experimental autoimmune myast
henia gravis (EAMG) was investigated. Immunization with acetylcholine
receptor (AChR) or injection of varying amounts of anti-AChR mAb 35 in
to young adult (10-12 wk) BN rats induced severe signs of EAMG includi
ng weight loss and decrement of muscle action potential, whereas aged
BN rats (120-130 wk) did not show any clinical signs of EAMG. Serum an
ti-AChR mAb titers were not significantly different in young and aged
rats up to 24 h after administration of mAb. No significant AChR loss
was demonstrated in aged rats, whereas similarly treated young rats sh
owed extensive AChR loss. In contrast to young rats, no degradation of
the postsynaptic membrane could be demonstrated by electron microscop
y in aged rats. C component C3 and C5b-9 membrane attack complex could
be demonstrated at the neuromuscular junction in both young and aged
mAb-treated rats. However, infiltrating macrophages and necrotic muscl
e fibers were seen only in young rats. These results suggest that the
postsynaptic membrane in aged rats is resistant to autoantibody attack
. AChR degradation by antigenic modulation may be less efficient in ag
ed rats as a result of altered AChR density and distribution or rigidi
ty of the postsynaptic membrane. Age-related resistance in the EAMG mo
del can provide more information about the factors that determine the
severity of myasthenia gravis. Manipulation of AChR density or lipid c
omposition of the postsynaptic membrane may be of therapeutic interest
in myasthenia gravis.