Antibodies against neuronal nicotinic receptor subtypes in neurological disorders

Abstract

Patients with myasthenia gravis (MG) have antibodies to the muscle nicotinic acetylcholine receptor (mAChR) which are responsible for their muscle weakness: but some patients with MG and other neuroimmunological disorders have autonomic symptoms. We characterised the neuronal forms of AChRs (nAChRs) into two neuroblastoma cell lines and developed immunoprecipitation assays to test for antibodies to the α7- and α3-containing nAChR subtypes, present in the autonomic ganglia. We then tested 70 sera samples from MG patients, 38 from subjects with other neurological diseases, and 30 from healthy individuals, for antibodies to these two forms of neuronal AChR subtypes. We used the α7 subtype extracted from the human neuroblastoma IMR32 cell line labeled with 125 I -αBungarotoxin (αBgtx), and the α3-containing subtype extracted from the human neuroblastoma SY5Y cell line labeled with 3 H -Epibatidine (Epi). Nine subjects (five MG, one GBS, one CIPD and two LEMS) were positive for the α7 subtype; and four for the α3-containing subtype (two MG patients, one LEMS and the same GBS patient). None of the MG patients with undetectable levels of antibodies against muscle AChR were positive. The patients with serum antibodies to α7 or α3-containing neuronal AChRs showed a range of clinical features including autonomic symptoms and thymoma in two MG patients. These results indicate that patients with MG and other immune-mediated disorders can have antibodies to neuronal AChRs, and that these may contribute to the clinical characteristics of the diseases.