Humoral immunity in myasthenia gravis: Biochemical characterization of acquired antireceptor antibodies and clinical correlations

The titer and characteristics of antiacetylcholine receptor antibody (A ChR-Ab) were investigated in 184 patients with myasthenia gravis. Mean A ChR-Ab titers of each clinical grade increased with the severity of the disease. A ChR-Ab was always of an IgG class. IgM (5 of 92) and IgA (2 of 48) class AChR-Ab were detected, but only concurrently with IgG and in low concentrations. IgG subclass 3 was not prominent. In 3 patients with A ChR-Ab titers in the normal range, blockade of bungarotoxin binding to receptor could still be demonstrated. A ChR-Ab from 6 patients was heterogeneous in affinity for receptor, reactivity with receptor from human ocular and gastrocnemius muscle, and blockade of toxin binding. A ChR-Ab was oligoclonal in 4 of 6 patients, as shown by concurrent production of A ChR-Ab IgG of both κ and λ types. Amniotic fluid and fetal cord serum did not interfere with antibody-receptor interaction. Variation in the pattern of weakness among patients was a function of both the heterogeneity of A ChR antibodies and the antigenic uniqueness of receptor complexes from different human muscles.