Myasthenia gravis is one of the best characterized human autoimmune disorders. Circulating autoantibodies to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction play a prominent part in the effector phase, that is, the immunoregulation. Indirect evidence, such as thymic abnormalities and the association with certain histocompatibility antigens (for example HLA-B8,-DR3) suggests a defect of immunoregulation at the level of thymus-dependent (T) lymphocytes. We report here on the isolation of autoreactive T cells from six patients with myasthenia gravis. From one of these patients, who is homozygous for HLA-DR3, we established a long-term T-cell line. The line cells are specific for purified fish and human AChR, display the surface phenotype of inducer/helper T cells and are genetically restricted to HLA-DR3. AChR-induced proliferation could be inhibited with two monoclonal antibodies against monomorphic DR determinants and also with DR3-specific alloantiserum.

We studied autoreactive acetylcholine receptor (AChR)-specific T cell lines from two patients with myasthenia gravis. Anti-AChR autoantibody production by peripheral blood mononuclear cells (PBM) from the donors of the T cell lines was measured with an enzyme-linked immunoadsorbent assay, using purified human AChR as antigen. Freshly isolated PBM produced barely detectable amounts of anti-AChR autoantibodies. If, however, autologous AChR-specific T cells were added to the cultures, the production of anti-AChR autoantibodies, and of total IgM and IgG, was markedly stimulated, depending on the number of T line cells and on the amount of AChR present in the cultures. AChR-specific functional helper T-lymphocytes may have a role in the immunoregulation of myasthenia gravis.

No abstract

In this randomized, 2-way crossover study, the potential for interaction was investigated between atorvastatin and ximelagatran, an oral direct thrombin inhibitor. Healthy female and male volunteers (n = 16) received atorvastatin 40 mg as a single oral dose and, in a separate study period, ximelagatran 36 mg twice daily for 5 days plus a 40-mg oral dose of atorvastatin on the morning of day 4. In the 15 subjects completing the study, no pharmacokinetic interaction was detected between atorvastatin and ximelagatran for all parameters investigated, including melagatran (the active form of ximelagatran) area under the plasma concentration versus time curve (AUC) and maximum plasma concentration, atorvastatin acid AUC, and AUC of active 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA) reductase inhibitors. Atorvastatin did not alter the melagatran-induced prolongation of the activated partial thromboplastin time, and both drugs were well tolerated when administered in combination. In conclusion, no pharmacokinetic or pharmacodynamic interaction between atorvastatin and ximelagatran was observed in this study.