Effect of thymectomy on peripheral lymphocyte subsets in myasthenia gravis: selective effect on T-cells in patients with thymic atrophy.

Abstract

Myasthenia gravis (MG) is an autoimmune disease affecting nicotinic acetylcholine receptors. The clinical improvement that follows thymectomy in some myasthenic patients implicates thymic factors as well in the pathogenesis of MG. We have studied circulating immunoregulatory T cell subsets before and after thymectomy in 11 adult patients with MG. Six patients had thymic hyperplasia and five patients had atrophic thymus at the time of thymectomy. Before thymectomy, patients who subsequently were shown to have an atrophic thymus, had lower lymphocyte counts than either patients later shown to have a hyperplastic thymus (1315 +/- 143 lymphocytes/mm3 vs. 2434 +/- 350 lymphocytes/mm3, p less than 0.01), or age-matched controls (1315 +/- 143 lymphocytes/mm3 vs. 2636 +/- 589 lymphocytes/mm3, p less than 0.02). Moreover, after thymectomy, in MG patients with an atrophic thymus, there was a significant rise in lymphocyte count (from 1315 +/- 143 lymphocytes/mm3 to 2279 +/- 292 lymphocytes/mm3, p less than 0.02) beginning 3 days postthymectomy and persisting for at least 6 weeks thereafter. In comparison, patients with a hyperplastic thymus showed no change in circulating lymphocyte counts (p greater than 0.1). Enumeration of lymphocyte subsets in MG patients with an atrophic thymus demonstrated normal B cell numbers before and after thymectomy (p greater than 0.1), whereas, T cells were significantly decreased before thymectomy compared with age-matched normal subjects (859 +/- 82 T cells/mm3 vs. 2215 +/- 545 T cells/mm3, p less than 0.05), and rose to near normal levels after thymectomy (1796 +/- 294 T cells/mm3, p less than 0.02 compared with prethymectomy levels). Using monoclonal anti-T cell antibodies 3A1, OKT4, and OKT8, we found that, before thymectomy in the atrophic thymus group, 3A 1+ T cells were significantly depressed compared with postthymectomy levels (620 +/- 173 cells/mm3 vs. 1627 +/- 331 cells/mm3, p less than 0.02) as were OKT4+ cells 436 +/- 88 cells/mm3 vs. 1112 +/- 63 cells/mm3, p less than 0.001), In contrast, no significant change was seen after thymectomy in the OKT8+ cell subset (p greater than 0.1). MG patients with an atrophic thymus had decreased plasma cortisol levels postthymectomy compared with prethymectomy levels, whereas thymectomy in MG patients with a hyperplastic thymus effected no change in plasma cortisol levels. These data demonstrate in MG patients with an atrophic thymus that thymectomy has an effect on the number of circulating T cells, and in particular, on those T cells expressing antigens 3A1 and OKT4. This effect may in part be mediated by changes in plasma adrenal corticosteroid levels after thymectomy or may be due to a factor produced by atrophic thymuses in MG.