title: Muscle acetylcholine receptors complexed with autologous IgG reflect seropositivity but not necessarily in vivo binding.
abstract: The diagnosis of acquired myasthenia gravis (MG) in apparently seronegative individuals is aided by finding immunoglobulin complexed to acetylcholine receptors (AChR) and a reduction in the number of binding sites for alpha-bungarotoxin (alpha-BTx) in nerve-muscle biopsies. In this study, we found that anti-AChR antibodies in extracellular fluids can complex with cytoplasmic epitopes of AChR in the process of muscle extraction. When normal muscle was briefly exposed to antibodies (greater than or equal to 0.3 nmol/l) in the initial step of tissue homogenization (before detergent extraction), membranous AChR became complexed with IgG. This was so even with a nonmyasthenogenic monoclonal antibody specific for the alpha-subunit's presumptive cytoplasmic segment 366-389. We also found that antibodies reactive with AChR's alpha-BTx binding region can significantly lower apparent yields of alpha-BTx binding sites extracted from muscle. Thus, the finding of IgG complexed to AChR extracted from biopsied muscle does not necessarily reflect in vivo binding but, nevertheless, is a sensitive indicator of AChR seropositivity in patients suspected to have MG.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN 55905.
authors.forename: M
authors.initials: M
authors.lastname: Sano
authors.forename: E H
authors.initials: EH
authors.lastname: Lambert
authors.forename: D J
authors.initials: DJ
authors.lastname: McCormick
authors.forename: V A
authors.initials: VA
authors.lastname: Lennon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002038:Bungarotoxins / Q000378:metabolism; D004576:Electromyography; D004594:Electrophysiology; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism*; D009045:Motor Endplate / Q000503:physiopathology; D009132:Muscles / Q000378:metabolism*; D009157:Myasthenia Gravis / Q000175:diagnosis / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012698:Serologic Tests
chemical_list: D000911:Antibodies, Monoclonal; D002038:Bungarotoxins; D007074:Immunoglobulin G; D011950:Receptors, Cholinergic