Acetylcholine receptor-alpha subunit expression in myasthenia gravis: a role for the autoantigen in pathogenesis?
Previous studies have shown increased expression of acetylcholine receptor-alpha (AChR-alpha) subunit transcripts in myasthenia gravis (MG) and experimental MG (EAMG), but none examined the functional properties of this overexpression. In this study we examined the mRNA and protein expression of AChR-alpha as well as the pattern of alpha-bungarotoxin labeling in muscle tissue from EAMG mice with varying disease severity. AChR-alpha expression was increased considerably in endplates from mice with severe EAMG, but it was distinct and greatly in excess of alpha-bungarotoxin labeling. This "aberrant expression" occurred in mice with morphologic endplate damage, and the pattern of complement and immunoglobulin deposition in muscle from these mice appeared to mirror the pattern of AChR-alpha expression. The loss of functional AChR in severe MG increases transcription of AChR-alpha mRNA, but the expressed protein is "functionally inert," failing to compensate for loss of AChR. This enhanced expression of AChR may play a role in driving the ongoing autoimmune response. Muscle Nerve 40: 279-286, 2009.
Sheng
Jian Rong
JR
Division of Neuromuscular Diseases, Department of Neurology and Rehabilitation, 912 South Wood Street, M/C 796, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Li
Liang Cheng
LC
Prabhakar
Bellur S
BS
Meriggioli
Matthew N
MN
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002038:Bungarotoxins / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005620:Freund's Adjuvant; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D012720:Severity of Illness Index; D014101:Torpedo
D000906:Antibodies; D002038:Bungarotoxins; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D005620:Freund's Adjuvant