Autoantibodies against M1 muscarinic acetylcholine receptor in myasthenic disorders.
Eur J Neurol
; 14(11): 1230-5, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17764462
ABSTRACT
The Lambert-Eaton myasthenic syndrome (LEMS), often associated with small-cell lung carcinoma (SCLC), is a disorder of acetylcholine (ACh) release from motor nerve terminals. In most patients, it is caused by autoantibodies against the P/Q-type voltage-gated calcium channels (VGCC) that trigger ACh release. However, these antibodies are not detected in approximately 15% of clinically and electrophysiologically typical cases. The M1-type pre-synaptic muscarinic ACh receptor (M1 mAChR) modulates cholinergic neuromuscular transmission by linking to P/Q-type VGCC, and may partially compensate for the reduced calcium entry. Immunoblotting against solubilized human M1 mAChR, we detected autoantibodies in (a) 14 of 20 (70%) anti-VGCC-positive LEMS patients; (b) all five anti-VGCC-negative LEMS patients, one of whose serum had previously passively transferred LEMS-type electrophysiological defects to mice; (c) all five LEMS patients with autonomic symptoms; (d) seven of 25 (28%) myasthenia gravis (MG) patients in whom increased ACh release partially compensates for post-synaptic defects; (e) none of 10 SCLC patients without LEMS. Although not proving primary pathogenicity of anti-M1 mAChR antibodies, the present results highlight their potential to affect synaptic compensatory mechanisms, more in LEMS than MG.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Síndrome Miastênica de Lambert-Eaton
/
Receptor Muscarínico M1
Limite:
Adult
/
Aged
/
Animals
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Eur J Neurol
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão