Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays

SUMMARY Anti-acetylcholine receptor (AChR) antibody was undetectable in 26/153 (17%) sera from myasthenia gravis patients assayed by standard RIA using human acetylcholine receptor. Eight of these were found to be positive with a modified protocol using a mixture of normal and denervated AChR, reducing the proportion of "negative" sera to 12%. Many of these were from patients with a short history; two such patients later developed low positive values. Anti-AChR without clinical evidence of myasthenia was found in one of three monozygotic twins of myasthenia gravis patients, and in one of thirty other first degree relatives of a further 17 patients. Anti-AChR is a valuable and highly specific diagnostic test which, with the assay used here, is positive in about 88% of patients with clinical features of myasthenia gravis In the last eight years it has been established that anti-acetylcholine receptor (anti-AChR) antibody is implicated in the loss of functional receptors in the post-synaptic membrane that underlies the defect in neuromuscular transmission in myasthenia gravis (for reviews see refs 1, 2). This antibody is usually detected by an immunoprecipitation assay in which AChR is labelled with '25I-alpha-Bungaratoxin (a-BuTx), a snake toxin that binds to AChR with high affinity. Anti-AChR antibody appears to be specific for myasthenia gravis3. Its clinical accep-tance as a diagnostic test is suggested by the steadily increasing number of serum samples sent to us for this assay (over 4,000 since 1980). In this paper we describe our assay methods and results in 153 myasthenia gravis cases studied before treatment by thymectomy