Humoral immunity in myasthenia gravis: clinical correlations of anti-receptor antibody avidity and titer.

Antibody to human acetylcholine receptor (AChR Ab) in myasthenia gravis (MG) correlates with clinical (Osserman) classification. Patients in remission R) or with ocular only (I) symptoms differed significantly from those with generalized disease (IIA, IIB, III, IV) (p less than 0.01, p less than 0.05 respectively). Patients with mild generalized disease (IIA) differed significantly from those with acute severe (III) or chronic severe (IV) disease (p less than 0.01). However, within each clinical class titers ranged over two or three orders of magnitude. This variation in AChR Ab titer for patients with similar diseases severity was not explained by differences in immunoglobulin class. All patients produced IgG AChR Ab and occasional patients produced IgM or IgA at less than 10% of their IgG titer. No IgM to IgG switch was identified. In MG patients negative for AChR Ab by immunoprecipitation assay, blockade of toxin binding to extracted human AChR could still be identified indicating antibody specificity to the toxin binding site. The avidity of AChR Ab for receptor assayed in six myasthenic patients with differing severities of disease, varied widely with T1/2 (time to half-maximal binding) ranges from 25 to 81 minutes. However, differences in AChR Ab avidity did not explain differences in severity of disease in patients with similar titers. AChR Ab was fractionated in six patients into IgG kappa and IgG lambda; in four patients AChR Ab activity could be demonstrated in both fractions. Thus, differences among MG patients as a group are due to production of several AChR Ab idiotypes, with individual patients being oligoclonal or polyclonal as well. Differences in IgG subclass (complement fixation) and site of attachment of AChR Ab to receptor subunits may resolve these differences.