Sixty patients with myasthenia gravis were examined prospectively by measuring serial titers of antibodies against human acetylcholine receptor, and these were correlated with a quantitative clinical score. Serial titers of antibodies detected by the standard immunoprecipitation assay (binding antibodies) correlated with the clinical score in most patients. Antibodies blocking the binding of alpha-bungarotoxin to receptors (blocking antibodies) were detected in 29 patients. Serial blocking antibody titers correlated with changes in muscle weakness less often than binding antibody titers. Titers of both classes of antibodies often followed a divergent course, suggesting that the autoimmune B-cell clones that formed these classes of antibodies may have been activated asynchronously.

No abstract

In this uncontrolled study, 104 patients with generalized myasthenia gravis treated with azathioprine for a median period of 29 months (range, 1 month to 12 years) were surveyed for possible adverse reactions. These occurred in 36 patients (35%) in the following order of frequency: hematologic (18%), gastrointestinal (13%), infectious diseases (13%), and elevation of liver enzymes (6%). No allergic skin reactions were observed. Azathioprine had to be discontinued temporarily in a total of 11 patients (11%) because of possible side effects. The cause of death in the nine patients who died during the period of observation (up to 12 years) was related to myasthenic crisis in two patients. In five patients, a malignant tumor was diagnosed (two carcinoma of the prostate, one ovarian carcinoma, one bronchial carcinoma, and one renal lymphoma) after 2.5 years, 6 months, 3 months, 5 years, and 6 years of treatment, respectively. A causal relationship seems unlikely in the first four cases, but cannot be excluded in the one case of late lymphoma.

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.

Mice were injected daily, for up to 10 weeks, with purified monoclonal immunoglobulin G from patients with myelomatous polyneuropathy or benign gammopathy. The animals developed a demyelinating polyneuropathy with slowed nerve conduction velocities. The putative antinerve factor may be an antibody since injection of Fab fragments from the monoclonal immunoglobulin G produced a similar demyelination. This provides evidence of a circulating factor in the serum of myeloma patients with polyneuropathy that reproduces typical features of the human disease on passive transfer. This disorder is thus distinguished from other neuropathies that occur as remote effects of malignant disease but have no identified pathogenic factors associated with them.