In myasthenia gravis, clinical and immunological improvement post-thymectomy segregate with results of in vitro antibody secretion by immunocytes
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abstract
In myasthenia gravis (MG), presence of pathogenic acetylcholine receptor antibodies (AchRAb) and thymic pathology are related. Our study assesses the long-term clinical outcome of thymectomy as a function of thymic pathologies, AchRAb levels in blood and the ability of immunocytes to secrete AchRAb ex vivo. We found that those patients who have thymocytes that secrete AchRAb in vitro have a greater decrease in their need for Mestinon over the 60 months of follow-up than the non-secretors (p = 0.04). Those patients whose cultured peripheral blood mononuclear cells (PBMC) secreted AchRAb also had a greater decrease in Mestinon requirements over the 60 months of follow-up than the non-secretors (p = 0.05), however, differences between the two groups at each individual assessment were not statistically significant. Serial post-op AchRAb measurements in sera of thymocyte and PBMC non-secretors showed no change from pre-op levels (< 10 nmol/l), while secretors had a reduction of more than 80% from pre-op levels, starting 6 months post-op. We also found that results of PBMC culture at time of thymectomy is a better predictor of response to thymectomy than serum AchRAb levels but inferior to results of thymocytes cultures. Patients with thymoma had the highest proportion of individuals secreting AchRAb from thymocytes in culture (78%), the shortest duration of disease (9 months) and showed the greatest trend toward improvement in clinical signs and symptoms post-op. We have thus demonstrated the long held suspicion that removal of actively secreting cells from the thymus at an early time in the disease confers the greatest benefit.
