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Transcription Factor TH1/TREG Regulates Glucocorticoid Expression In Children Myasthenia Gravis Pathogenesis

Posted on:2012-07-07Degree:MasterType:Thesis
Country:ChinaCandidate:Z X HuangFull Text:PDF
GTID:2154330335987170Subject:Academy of Pediatrics
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Objective: To explore Th1 / Treg cells transcription factor T– bet and FOXP3 mRNA and related cytokines interferon - gamma (IFN- gamma), interleukin-6 (IL-6) and transformation growth factor beta 1 (TGF-β1) in children myasthenia gravis pathogenesis. And to understand the alterative of humoral and the cellular immunity index in myasthenia gravis (MG) patients, to further explore the relationship with ocular myasthenia gravis.QMethods: The mRNA expression of T-bet and FOXP3 were detected in the peripheral blood mononuclear cells of 31 MG children patients and 20 healthy children by using RT-PCR. The concentration of related cytokines IFN-γ,IL-6 and TGF-β1 was applied by ELISA. The humoral immunity index(IgG and IgG subclasses) were detected by scattering immunoturbidimetric methods, and the change of lymphoid cell index(CD3~+,CD19~+,CD4~+,CD8~+,CD4~+:CD8~+) was detected by flow cytometry. Results: Compared with the healthy control group, the T-bet mRNA expression was significantly higher in children with MG (P <0.05). In MG group FOXP3 mRNA expression is significantly higher than that in control group (P < 0.05). The ratio between T-bet mRNA and FOXP3 mRNA expression was significantly higher in MG groups than in healthy controls. There was no significant differences of the concentration of IFN-gamma, IL-6 and TGF-beta 1 in the two groups. There were 11 MG patients with aberrant IgG (35.48%), 10 patients with abnormal IgG1 (32.26%), 8 patients with abnormal IgG2 (25.81%), 21 with abnormal IgG3 (67.74%), 12 with abnormal IgG4 (38.71%). There were 5 patients with abnormal CD19~+, and 1 patient with abnormal CD4~+. However, the expressions of CD3~+, CD8~+, and CD4~+/ CD8~+ were normal.Conclusion: T-bet mRNA and FOXP3 mRNA expression is abnormal in children with MG, indicating that Th1 and Treg cells are involved with the pathogenesis of MG. The concentrations of IFN-gamma, IL-6 and TGF-beta 1 in MG patients have no obvious abnormity, indicating that the children immune dysfunction is light. The humoral immunity index exists a variety of degree, while the cellular immunity index is not obviously abnormal, suggesting more prominent disorder in the humoral immunity than in the cellular immunity in MG children, which is consistence with the slight clinical presentation in children with ocular myasthenia gravis. Objective: To investigate the effect of glucocorticoid treatment on the expression of transcription factor Th1/Treg, T-bet and FOXP3, and the related cytokines in children with myasthenia gravis (myasthenia gravis, MG),to further understand the mechanism.Methods: The mRNA expression of T-bet and FOXP3 in the peripheral blood mononuclear cells was detected by RT-PCR in 52 MG patients and 20 healthy children. The concentration of the related cytokines, IFN-γIL-6 and TGF-β1, were analyzed by ELISA.Results: Both the mRNA expression of T-bet and FOXP3 were significantly higher (P <0.05) in MG children compared with the healthy control group. However, there were no significant difference between MG children pre- and post-hormone treatment. The ratio between T-bet mRNA and FOXP3 mRNA expression was significantly higher in post-hormone treatment than in pre-hormone treatment in healthy controls. IFN-γconcentration was significantly higher (P <0.05) in hormone therapy group compared with the healthy control group and pre-hormone treatment group, while no significant difference was in the healthy control group and the before treatment group. Among the three groups, the level of IL-6 and TGF-β1 was not significantly different.Conclusion : T-bet mRNA and FOXP3 mRNA expression is abnormal in children with MG, which the immune function restore to some extent after hormone treatment. The IL-6 and TGF-β1 levels are almost normal after hormone treatment. The increased IFN-γlevels in post-horomone treatment suggest that IFN-γmight play a role in protection of the body in some cases.
Keywords/Search Tags:children with myasthenia gravis, T-bet, FOXP3, IFN-γ, glucocorticoid
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