Role of the target organ in determining susceptibility to experimental autoimmune myasthenia gravis.
Injection of anti-AChR antibodies in passive transfer experimental autoimmune myasthenia gravis (EAMG) results in increased degradation of acetylcholine receptor (AChR) and increased synthesis of AChR alpha-subunit mRNA. Passive transfer of anti-Main Immunogenic Region (MIR) mAb 35 in aged rats does not induce clinical signs of disease nor AChR loss. The expression of the AChR subunit genes was analyzed in susceptible and resistant rats. In aged EAMG resistant rats, no increase in the amount of AChR alpha-subunit mRNA was measured. In vivo AChR degradation experiments did not show any increase in AChR degradation rates in aged resistant rats, in contrast to young susceptible rats. Taken together, these data demonstrate that resistance of the AChR protein to antibody-mediated degradation is the primary mechanism that accounts for the resistance to passive transfer EAMG in aged rats.
Hoedemaekers
A
A
Maastricht University, Department of Immunology, The Netherlands.
Bessereau
J L
JL
Graus
Y
Y
Guyon
T
T
Changeux
J P
JP
Berrih-Aknin
S
S
van Breda Vriesman
P
P
De Baets
M H
MH
D000375:Aging / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015551:Autoimmunity / Q000276:immunology*; D001706:Biopsy; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000276:immunology; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000276:immunology / Q000294:innervation / Q000473:pathology; D009157:Myasthenia Gravis / Q000276:immunology*; D009469:Neuromuscular Junction / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D011950:Receptors, Cholinergic / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D012584:Sciatic Nerve / Q000601:surgery; D013569:Synapses / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D011950:Receptors, Cholinergic