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Biomedical subjects

K Isakovic

Publications and source records attributed to K Isakovic.

6 recordsLinked to original sources

Leflunomide prevents the development of experimentally induced myasthenia gravis.

Myasthenia gravis is an autoimmune disease in which autoantibodies specific to the acetylcholine receptor (AChR) are formed, leading to a gradual destruction of the receptors in muscles that are responsible for picking up nerve impulses, and results in weakness and eventual loss of muscle function. The novel immunomodulating drug leflunomide (HWA 486) has been shown to be very effective in preventing and halting ongoing disease in an array of experimental autoimmune disorders and reactions leading to organ graft rejection. Further, recent data from phase II clinical trials indicate that this drug is efficacious and is safe in humans with rheumatoid arthritis. In the studies reported here, we found that rats immunized with AChR-protein and not receiving leflunomide developed experimental myasthenia gravis (EMG) between day 7 and 11 post-immunization, and about 79% of these animals expressed clinical signs of disease. Treatment of AChR-protein immunized rats with leflunomide, from the day of disease induction, totally suppressed the development of EMG. Thus, the results we have obtained using leflunomide in EMG indicate that this drug could be beneficial in combating myasthenia gravis in humans.

Animals↗

Epithelial cells and macrophages in myasthenia gravis thymus culture.

Monolayer culture of thymic nonlymphoid cells derived from female patients with myasthenia gravis (MG) and individuals who underwent heart surgery was established to investigate the cellular composition of the thymic microenvironment and the interaction of nonlymphoid cells with autologous thymocytes. Thymic epithelial cells were identified by immunoperoxidase staining using monoclonal antibodies (mAbs) specific for cytokeratin and MR6 and MR19 antigens expressed on cortical and medullary epithelial cells, respectively. Macrophages were characterized by determination of alpha-naphthyl acetate esterase activity and detection of M1 antigen by mAb. It was demonstrated that in MG thymus cultures the number of cortical MR6+ epithelial cells is significantly reduced, and the ability of the remaining MR6+ cells to bind autologous thymocytes is markedly affected. On the other hand, the number of macrophages and the interaction of those cells with thymocytes were similar in MG and control thymus cultures. Since MR6+ epithelial cells are numerically and functionally affected in MG, maturational events of T cells occurring in the inner cortex may be altered. The mechanisms underlying the induction and expansion of T helper clones in MG are discussed.

Adolescent↗