IngentaConnect Autoantibodies against M1 muscarinic acetylcholine receptor in my...

Authors: Takamori, M.¹; Motomura, M.²; Fukudome, T.³; Yoshikawa, H.⁴

Source: European Journal of Neurology, Volume 14, Number 11, November 2007 , pp. 1230-1235(6)

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.

Keywords: autoimmunity; calcium channel; Lambert-Eaton myasthenic syndrome; muscarinic acetylcholine receptor; myasthenia gravis

Document Type: Research article

DOI: 10.1111/j.1468-1331.2007.01931.x

Affiliations: 1: Neurological Center, Kanazawa-Nishi Hospital, Kanazawa, Japan 2: First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan 3: Department of Clinical Research, Nagasaki Medical Center of Neurology, Kawatana, Japan 4: Department of Neurology, Kanazawa University Hospital, Kanazawa, Japan

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Autoantibodies against M1 muscarinic acetylcholine receptor in myasthenic disorders