Myasthenia gravis: reactivation of clinical disease and of autoimmune factors after discontinuation of long-term azathioprine

In 15 patients with myasthenia gravis who were in stable clinical remission while receiving azathioprine, we monitored disease severity and serial autoantibody titers before and after discontinuation of azathioprine. Cellular immunoreactivity against tuberculin (PPD) and against Torpedo acetylcholine receptor (AChR) was measured serially in 11 patients. Eight of 15 patients (53%) had a clinical relapse after 3 to 11 months, necessitating the reinstitution of immunosuppressive treatment in 6 patients. Seven patients have remained clinically stable during an observation period of 20 to 40 months. Anti-AChR autoantibody titers correlated closely with the clinical course in the majority of patients, and rose markedly in 7 of the 8 patients who relapsed. Cellular stimulation indices correlated less closely with the clinical severity. Only in 3 patients did the clinical score, antibody titer, and cellular stimulation index rise concurrently. In 4 patients who had high cellular stimulation indices after the discontinuation of azathioprine, it was possible to isolate AChR-reactive inducer/helper T lymphocytes.