Study On Fas Expression Of Lymphocytes Subgroup And The Level Of IFN-γ,TNF-α And AchRAb Of Patients With Myasthenia Gravis

Background and Ojectives: Myasthenia gravis (MG) is one ofautoimmunity diseases, which is mainly mediated by the effect of the acetylcholine receptor antibody (AchRAb) against acetylcholine receptor on the postsynaptic membrane of the neuromuscular junction. Youngsters are the susceptibleness. The pathogens is not well understood.Many of those cases have been found with the abnormality in humoral and cell immunity or with thynrus tumor or hyperplasia. Fas molecule is one of the important relative apoptosis molecules on the surface of cell membrane. Specilly, it has the close nelation to T-lymphocytes cytotoxicity , induce cell death and thymus cells negative election. The recent studies showed that in children cases and animal model, there were Fas gene mutation and Fas molecule expression disorder. To investigate the roles of CD4, CD8 and Fas molecules on the pathogenesis of myasthenia gravis, the cell surface expressions of CD4, CD8 and Fas molecules on peripheral blood lymphocyte, Subgroup in advanced children MG cases were tested by fluorochrome coupled monoclonalantibodies(FITC-anti-Fas, PE-anti-CD4, Cy-anti-CD8) and cytometry analysis. This study is intended to elucidate the pathogenesis of MG and supply the theorical basis to therapy.Methods: Thymocytes were obtained from the thymus tissue in 10 patientswith MG and 10 normal controls without auto-immunity defects, The lymphocytes were isolated by mechanical method. The periphenal lymphocytes were separated with lymphocyte separating solusion ,and the serum was separated from the un-anticoagulation blood . The cell surface expressions of CD4, CD8 and Fas molecules on lymphocyte were tested by fluorochrome coupled monoclonal antibodies (FITC-anti-Fas, PE-anti-CD4,Cy-anti-CD8). The serum soluble Fas (sFas) and TNFαwere detected by ELISA.The statistical analysis was down by using the SPSS 10.0 software. Whenαequal than 0.05 the value was as the significant.Results: 1. The results showed that the comparison with those of controls,the rate of double positive cells in the CD4~+CD8~+ were lower significantly (42.12±9.70) than those of the controls(85.25±4.53), but the CD8~+ were higher(22.50±8.65) .The percentage sate both the CD4~+Fas~+ and CD8~+Fas~+ have a significant defferent in patients with MG , P<0.01.2. The rate of Fas expression (36.31±5.68) and CD4~+CD8~- thymocytes (65.27±7.25) in children patients with MG were significantly increased, but that of single positive CD4~-CD8~+ thymocytes in children patients with MG decreased as compared with controls, P<0.05.3. The sFas level in the children MG cases serum was higher than those in controls,then a positive correltion between the level of serum sFas and AchRAb.4. The increase of the serum IFN-γ,TNF-αin children MG cases has a positive correlation with its level of serum AchRAb.Conclusion: 1. The abnormal expression of Fas in the thymocyte tissueand sFas in periphenal lymphocyte and serum in patients with children MG may participates in controlling the thymocyte apoptosis. The formation of the self-reaction T tymphocyte may be one of important factors in the pathogenesis of MG.2. Cytokines of IFN-γ,TNF-αplay an important role in pathogenesis children myasthenia gravis.