The Study Of Thymectomy On Peripheral SjTREC And Immunologic Effects In Myasthenia Gravis Patients

Myasthenia gravis (MG) is an autoimmune disorder mainly caused by antibodies to the muscle acetylcholine receptors (AChR) at the neuromuscular. The muscular weakness and fatigability are the hallmarks of myasthenia gravis. Myasthenic crisis is life-threating episode of respiratory or bulbar paralysis. The factors that initiate and maintain the autoimmune response in myasthenia gravis are not yet known. The thymus has been implicated as a possible site of origin because approximately 80-90 percents of patients have thymic abnormalities. Of these, 65-75 percents have lymphofollicular hyperplasias and 15 percents have thymomas. The human thymus is the primary site of T cells maturation and development, shortly after birth, the thymus undergoes a life long process of involution whereby the organ is replaced by adipose tissue, suggesting that the adult thymus may not be function. However, recent data suggest that despite thymic involution, pockets of active T cells synthesis (thymopoiesiss) still exist. This finding can be exploited to reconstitute the immune system by enhancing thymic function in conditions that causing T cells depletion, such as the acquired immunodeficiency syndrome or intensive chemotherapy. Therefore, monitoring thymic function by measuring new T cell synthesis becomes a critical prerequisite in immune reconstitution studies. However, specific phenotypic markers that distinguish recent thymic emigrants (RTEs) from the rest of the peripheral T cells do not exist. Nevertheless, T cell receptor excision circles (TRECs) can be used as a tool to monitor the function of thymus. TRECs are generated during the T cell receptor gene rearrangement that can be specifically correlated with RTEs. Someone has reported that the thymectomized and non-thymectomized MG patients had lower TRECs levels than did age-matched normal subjects, which demonstrated that MG itself or treatment for MG decreased thymopoiesis for the MG patients had received immunomodulating medications. At present no further reports are published about the change of MG thymus function. MG is known to be due to antibody-mediated autoimmune attack directed against acetylcholine receptors. With the development of modern immunology the roles of T cells are paid intensive attention in the occurrence of MG. The inverse proportion of CD4+T and CD8+T cells and abnormal expression of related cytokines closely correlated with the production autoantibodies. Autoreactive T cells escaped from thymus "negative selection" can recognize self-tissue and result in autoimmune disease. CD4+CD25+ regulatory T cells have been the objects of intensive studies because their functions appear critical in maintaining self-tolerance. Thus CD4+CD25+ regulatory T cells provide the opportunity to determine whether alternation of these populations are involved in the induction of human autoimmune disorder. Although thymectomy is the most important treatment in MG patients, its mechanism is not clear until now. MG is also the only clinical setting of therapeutic thymectomy is routinely performed. Therefore, we used this clinical setting of therapeutic thymectomy to study the change of thymus function and the impact of thymus removal on immune system in MG patients. For these reasons, we focused on the therapeutic thymectomy in MG patients to study the following parts: 1. The morphology, perivascular space and thymocytes subsets of the thymus in MG patients were observed by electron-microscope, immunohistochemistry staining and flow cytometer separately. 2. The sjTREC- RAG2 gene was cloned to pMD 18-T vector. The sjTREC of peripheral blood in MG patients was measured by real-time fluorescent quantitative polymerase chain reaction. 3. The T cells subsets and related cytokines IL-4 and IFN-γ, CD4+CD25+ regulatory T cells, immunoglobulins, complements and AChR antibodies in MG patients were measured. The clinical responses to thymectomy in MG patients were assessed in our department.The experimental results showed that: 1. The MG thymus appeared abnormal morphology. Th...