Age-related resistance to experimental autoimmune myasthenia gravis in rats.
The influence of age on the induction of experimental autoimmune myasthenia gravis (EAMG) was investigated. Immunization with acetylcholine receptor (AChR) or injection of varying amounts of anti-AChR mAb 35 into young adult (10-12 wk) BN rats induced severe signs of EAMG including weight loss and decrement of muscle action potential, whereas aged BN rats (120-130 wk) did not show any clinical signs of EAMG. Serum anti-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 showed extensive AChR loss. In contrast to young rats, no degradation of the postsynaptic membrane could be demonstrated by electron microscopy 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 muscle 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 aged rats as a result of altered AChR density and distribution or rigidity of the postsynaptic membrane. Age-related resistance in the EAMG model can provide more information about the factors that determine the severity of myasthenia gravis. Manipulation of AChR density or lipid composition of the postsynaptic membrane may be of therapeutic interest in myasthenia gravis.
Graus
Y M
YM
University of Limburg, Department of Immunology, Maastricht, The Netherlands.
Verschuuren
J J
JJ
Spaans
F
F
Jennekens
F
F
van Breda Vriesman
P J
PJ
De Baets
M H
MH
D000375:Aging / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D004576:Electromyography; D005260:Female; D007113:Immunity, Innate; D007116:Immunization, Passive; D008264:Macrophages / Q000276:immunology; D008297:Male; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology; D009469:Neuromuscular Junction / Q000648:ultrastructure; D051381:Rats; D011914:Rats, Inbred BN; D011950:Receptors, Cholinergic / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D009435:Synaptic Transmission
D000911:Antibodies, Monoclonal; D011950:Receptors, Cholinergic; D003165:Complement System Proteins