Autoantibodies against M1 muscarinic acetylcholine receptor in myasthenic disorders

Eur J Neurol. 2007 Nov;14(11):1230-5. doi: 10.1111/j.1468-1331.2007.01931.x. Epub 2007 Aug 31.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Animals
  • Autoantibodies / biosynthesis*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Female
  • Humans
  • Lambert-Eaton Myasthenic Syndrome / immunology*
  • Male
  • Middle Aged
  • Receptor, Muscarinic M1 / immunology*

Substances

  • Autoantibodies
  • Receptor, Muscarinic M1