Acetylcholine Receptor Antibodies
Antibodies to the acetylcholine receptor (anti-AChR) are present in a very high proportion of patients with the neuromuscular transmission disorder, myasthenia gravis (MG). Myasthenia gravis is clinically characterized by generalised muscle weakness with fatiguability (generalised MG). This condition also frequently involves and is isolated to the extraocular muscles, leading to the symptom of double vision (ocular MG). Anti-AChR autoantibodies interfere with normal neuromuscular function by binding to the post-synaptic acetylcholine receptor. The disease has a prevalence of approximately 5 per 100,000 individuals and can occur at any age. In women, the disease usually presents between the ages of 20 and 40 years, while disease onset in men typically occurs later in life. There is also a peak of incidence in old and very old age; thus neither age nor sex are precluding factors for anti-AChR screening. MG also has a strong association with tumours of the thymus (thymoma). Approximately 90% of patients with generalised MG have these antibodies detectable in their serum. In patients with purely ocular MG the proportion of positive patients is lower at approximately 70%. A positive result is up to 99% specific for MG. Antibody titres tend to be higher in females and a correlation between antibody titre and the degree of muscle weakness has been observed in longitudinal studies in individual patients; however titre cannot be used to compare severity between individuals. In individual patients with established myasthenia gravis, anti-AChR antibody titres tend to rise several weeks before exacerbations. Remission after thymectomy is associated with a progressive decline in antibody titres. Consequently, serial measurements of acetylcholine receptor antibodies can be useful in monitoring disease progression, as well as the effects of treatment. Anti-AChR antibodies can also very rarely be positive in uncomplicated thymoma, primary lung cancer, and in patients with autoimmune liver disease. A negative anti-AChR antibody test does not preclude the diagnosis of MG. Anti-AChR seronegative cases exist, and a proportion of these have antibodies to a neuromuscular protein termed MuSK (muscle specific kinase). In a clinically related condition, the Lambert-Eaton myasthenic syndrome (LEMS), antibodies to a presynaptic protein (the voltage gated calcium channel, VGCC) are present. The anti-AChR test is conducted by a radioimmunoprecipitation assay using radio-iodinated bungarotoxin bound to acetylcholine receptors that have been extracted from an acetylcholine receptor expressing cell line. 125I-AChR is incubated with test sera and any resulting complex of labelled receptor and receptor antibody is then immunoprecipitated with anti-human IgG. After a centrifugation and wash step the precipitate is counted, and the result is reported as nmol/litre of anti-AChR antibody. The assay is conducted once per week and results are despatched the following day. 1ml of serum is required for this investigation.