Detection and characterization of blocking-type anti-acetylcholine receptor antibodies in sera from patients with myasthenia gravis.
We developed a highly sensitive, convenient assay for measuring blocking-type anti-acetylcholine receptor antibodies, which inhibit the binding of 125I-labeled alpha-bungarotoxin (alpha-BuTx) to the acetylcholine receptor (AChR). This procedure detected inhibitory activities in sera from 76% of patients with myasthenia gravis. Results of an experiment done with synthetic peptide corresponding to the alpha-BuTx binding region in the alpha-subunit of Torpedo AChR suggested that this inhibition is due to nonspecific steric hindrance caused by the binding of antibodies to a region other than the alpha-BuTx site, rather than by direct binding to the latter site. The inhibitory activities of the blocking-type antibodies and the titers of non-blocking-type antibodies were correlated. Moreover, the blocking-type antibodies could dissociate 125I-labeled alpha-BuTx from 125I-labeled alpha-BuTx-human AChR complex, and their dissociation activities showed good correlation with the inhibitory activities.
Hara
H
H
Clinical Research Center, Utano National Hospital, Kyoto, Japan.
Hayashi
K
K
Ohta
K
K
Itoh
N
N
Nishitani
H
H
Ohta
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001665:Binding Sites; D002038:Bungarotoxins / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000150:complications / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011863:Radioimmunoassay; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000378:metabolism; D013945:Thymoma / Q000150:complications / Q000276:immunology; D013953:Thymus Neoplasms / Q000150:complications / Q000276:immunology; D014101:Torpedo
D001323:Autoantibodies; D002038:Bungarotoxins; D010455:Peptides; D011950:Receptors, Cholinergic