Monoclonal Antibodies as Probes for Acetylcholine Receptor Epitopes in Thymuses and Thymic Epithelial Tumors of Patients with Myasthenia Gravis and Nonmyasthenic Controls

Myasthenia gravis ( M G ) is associated with heterogeneous thymus changes. Thymitis with lymphoid follicular hyperplasia (LFH) is found in 60-80% and thymoma in 10% of the patients. These divergent morphologic findings correspond to different clinical groups of patients with MG and might be related to various mechanisms of tolerance breakdown. A possible link between them could be the expression of acetylcholine receptors ( AChRs) or AChR-like epitopes (Eps) in both tumor-free thymuses and thymic epithelial tumors of patients with MG. Previously a-bungarotoxin (a-Bgt) binding sites were demonstrated on thymic myoid cells (MyCs)' and epithelial cells (ECs),' and recently a cobrotoxin binding protein was isolated from MG-associated thymomas.' However, a-Bgt binding may not sufficiently prove the presence of complete A C ~ R S . ~ Therefore, we applied monoclonal antibodies (mAbs) for an in situ demonstration of AChR Eps on thymic cells. Normal thymuses of 10 nonmyasthenic persons (age 2 days-57 years), thymitis with LFH in 13 patients with M G (age 8-45 years), thymic epithelial tumors of 8 patients with MG (age 36-72 years), and 6 patients without M G (age 47-72 years) were studied by immunohistochemistry on cryostat section. MAbs 152, 153, and 155'