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Acetylcholine receptor‐α subunit expression in myasthenia gravis: A role for the autoantigen in pathogenesis?
Author(s) -
Sheng Jian Rong,
Li Liang Cheng,
Prabhakar Bellur S.,
Meriggioli Matthew N.
Publication year - 2009
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21371
Subject(s) - myasthenia gravis , acetylcholine receptor , endocrinology , medicine , pathogenesis , messenger rna , acetylcholine , neuromuscular junction , protein subunit , biology , receptor , autoimmune disease , immunology , antibody , gene , biochemistry , neuroscience
Abstract Previous studies have shown increased expression of acetylcholine receptor‐alpha (AChR‐α) 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‐α as well as the pattern of α‐bungarotoxin labeling in muscle tissue from EAMG mice with varying disease severity. AChR‐α expression was increased considerably in endplates from mice with severe EAMG, but it was distinct and greatly in excess of α‐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‐α expression. The loss of functional AChR in severe MG increases transcription of AChR‐α 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