Serum Antibodies Myasthenia Gravis

Several types of antibodies are found in the majority of patients with MG and include forms directed against the acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK). Ten percent of patients with acquired, presumably immune-mediated MG do not have detectable serum antibodies to AChR or MuSK. In these seronegative patients, the diagnosis is based on the clinical presentation, the response to cholinesterase inhibitors and electrodiagnostic findings.

Anti-striational muscle antibodies (Str-Abs), which react with contractile elements of skeletal muscle, are not pathogenic. They are found in more than 90% of MG patients with thymoma, and in one-third of patients with thymoma who do not have MG. One-third of MG patients without thymoma also have these antibodies; they are more frequent in older patients and in those with more severe disease. Str-Abs are also elevated in other disorders including autoimmune liver disease and infrequently in Lambert-Eaton syndrome and in primary lung cancer. Str-Abs are rarely, if ever, elevated in MG in the absence of acetylcholine receptor antibodies and are therefore of limited use in confirming the diagnosis. The main clinical value of Str-Abs is in predicting thymoma: 60% of patients with MG with disease onset before age 50 who have elevated Str-Abs acetylcholine receptor antibodies (AChR-Abs) have thymoma.

At least 85% of patients with acquired generalized myasthenia and 54% with ocular myasthenia have serum antibodies that bind human acetylcholine receptor (AChR) although there is wide variation in reported studies. The serum concentration of AChR antibody varies widely among patients with similar degrees of weakness and its level cannot predict the severity of disease in individual patients. Approximately 10% of patients who do not have binding antibodies, have other antibodies that modulate the turnover of AChR in tissue culture. The concentration of binding antibodies may be low or absent at symptom onset and become elevated later. AChR binding antibodies concentrations are sometimes increased in patients with systemic lupus erythematosus, inflammatory neuropathy, amyotrophic lateral sclerosis, rheumatoid arthritis taking D-penicillamine, thymoma without myasthenia gravis, and in normal relatives of patients with myasthenia gravis. False positive tests are reported when blood is drawn within 48 hours of a surgical procedure involving the use of general anesthesia and muscle relaxants. In general, an elevated concentration of AChR binding antibodies in a patient with compatible clinical features confirms the diagnosis of myasthenia gravis, but normal antibody concentrations do not exclude the diagnosis.

Antibodies to muscle-specific receptor tyrosine kinase (MuSK), a surface membrane component essential in the development of the neuromuscular junction, have recently been identified and are found in up to 40% of MG patients who are seronegative for AChR antibodies. Another small percentage of these seronegative patients have antibody to the agrin receptor low-density lipoprotein receptor–related protein 4 (LRP4). These patients typically will have prominent weakness of the neck, oro-bulbar and sometimes respiratory musculature, are often poorly responsive to cholinesterase inhibitors.