In vitro T-cell dependent B-cell activity in myasthenia gravis.

The in vitro T-cell dependent B-cell activity was analysed in 34 patients with myasthenia gravis and in 16 controls by culturing 1 X 10(6) peripheral blood lymphocytes for 8 days with or without pokeweed mitogen (PWM) and measuring the amounts of IgG and IgM released into the culture supernatant. Increased production of IgG in the unstimulated cultures was found in 20 patients, 8 of whom also produced increased amounts of IgM. Upon PWM stimulation the patients produced normal amounts of IgG. The IgM production, however, was decreased in the patient population compared to the controls. Only one of the controls produced more IgG than IgM, either unstimulated or during PWM stimulation. In contrast 10 patients produced more IgG than IgM in the unstimulated cultures and 15 patients did so during PWM stimulation. The 'spontaneous' production of immunoglobulins was not measurable before 4 days of culture and was not the result of in vivo activated B-cells. We suggest that the increased 'spontaneous' immunoglobulin production and the decreased production of IgM during PWM stimulation may be a result of abnormal T-cell activity. The abnormalities found were not related to disease activity, the presence of multiple autoantibodies in the serum, steroid therapy or previous thymectomy. Besides these abnormalities, patients not treated with immunosuppressive drugs also showed decreased PWM induced IgG synthesis.

Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 3. The effect of thymectomy.

The clinical condition and the serum levels of antibodies to acetylcholine receptor protein were followed in 30 patients with myasthenia gravis before and in a period varying from 2 to 4 (mean 3) yr after thymectomy. Twenty-five patients improved in the 2 yr following thymectomy. A highly significant correlation was found between the change in clinical condition and the change in antibody levels. Only 3 patients improved without a fall of antibody level. Prethymectomy antibody levels were positively correlated with the severity of the clinical condition and with the degree of thymus hypertrophy.

Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 1. Relation to clinical parameters in 250 patients.

We examined the significance of the presence or absence of anti-acetylcholine receptor (anti-AChR) antibodies in 250 myasthenia gravis (MG) patients and the relation between clinical features and anti-AChR levels. We found high anti-AChR levels in 2 out of 11 thymoma patients without MG, while 37 out of 250 MG patients had no detectable anti-AChR. The absence of these antibodies was related to purely ocular disease and to steroid therapy and/or thymectomy. Differences in anti-AChR levels did not correspond significantly to differences in disease activity when single measurements in patients were analysed. However, the results were influenced by both the presence or absence of a thymoma, the age at onset of disease and by steroid therapy. The thymic pathology and age at onset seemed to act independently. Early onset of disease was associated with high anti-AChR levels and absence of antibodies to striated muscle (anti-SM), whereas late onset was associated with low anti-AChR and the presence of anti-SM. Thymomas both have high anti-AChR and high anti-SM. The effect of steroid therapy on antibody levels was seen in all patient groups but was strongest in thymoma patients with early onset of disease.

Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 2. Clinical and serological follow-up of individual patients.

Circulating antibodies to acetylcholine receptor protein (anti-AChR) were measured in the sera collected from 75 patients (53 women, 22 men, ages 9-83 year, 20 with a thymoma) with myasthenia gravis (MG) during 5-44 (mean 25) months. The clinical state of each patient was graded on a 6-point scale. Anti-AChR concentrations were measured by a radioimmunoassay with human antigen. We analysed the relation between the change in clinical state and the change in anti-AChR concentration in 155 periods (1-7, mean 2.1 per patient). The change in clinical state is given as the difference in score at the onset and at the end of this period. The change in anti-AChR concentration is expressed as the percentage of the original concentration at the onset of the period. The results were analysed in relation to the therapy and to the severity of the MG at the onset of each period. A strong correlation between a change in anti-AChR concentration and a change in clinical condition existed during treatment with prednisone or immunosuppression and in the period after thymectomy, while a weaker correlation was present in periods without immunosuppression. In only 3 patients did the changes in anti-AChR concentration precede the clinical change. No changes in anti-AChR concentrations were found if improvement was due to the effect of anticholinesterases or if deterioration was caused by infection or emotion. The serial measurement of anti-AChR may be a valuable method of following the basic trend of the MG in severely affected patients.