AGE-RELATED RESISTANCE TO EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS IN RATS

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.