Acetylcholine receptor antibody: clinical and experimental aspects

Anti-acetylcholine (ACh) receptor antibody is the specific antibody in myasthenia gravis (MG). Groups of patients distinguished by thymic pathology and age of onset have shown differences in sex and HLA antigen incidence and in anti-ACh receptor antibody levels. Group differences in the characteristics of this antibody, including the percentage of kappa and gamma light chains, IgG subclass and reactivity with other ACh receptor preparations, were detected only in patients with ocular MG. This group alone showed a possible association with Gm allotype in Caucasians; the anti-ACh receptor antibody had a greater proportion of kappa light chain and better reactivity with human ocular ACh receptor than did generalized MG. The results indicate heterogeneity of this disease. Thymic cells from myasthenic patients with thymic hyperplasia spontaneously synthesize anti-ACh receptor antibody in culture and, after irradiation to abrogate antibody production and any suppressor effects, can selectively enhance the synthesis of anti-ACh receptor antibody by autologous blood lymphocytes in co-culture. The cell types that underlie these responses have been investigated by deleting cell subsets by complement-mediated lysis using monoclonal antibodies. Neither cortical (NA1/34+) thymocytes nor mature T cells (MBG6+) are essential for antibody production in vitro by thymic cells. The enhancement of antibody production by irradiated thymic cells may depend on antigen-presenting cells not expressing the HLA-DR surface marker, or possibly antigen-specific helper T cells, or both.