The Role Of IL-17 And CXCL-13 In Pathogenesis Of Experimental Autoimmune Myastheia Gravis And Thymoma With MG

Background and objective Myasthenia gravis(MG) is mediated by aectylcholine receptor antibody.At present,there is not any effective immuno-therapy for myasthenia gravis. Terefore an urgent need to clear its pathogenesis.. Experimental autoimmune myastheia gravis(EAMG)is a perfect model for MG,cause it has similar immunopathofogic manifestations,electrophysiology and clinical compare to MG.Injection of immune with The electric eel organ is a widely used path to establish EAMG model.While The electric eel organ is very difficult to get in internal.We need to find out a model that simple and quick,with a high success rate of establish.Research shows that Th17 plays a very important role in pathogenesis of EAMG and MG. Our previous studies have demonstrated that Th17 cells, rather than Th1 cells, assist B cell secrete autoantibody independence. Previous studies show that CXCL13 plays an important role in B cell homing and migration to lymphoid tissue in T and B cell areas. It is reported that human Th17 cell clones and express CXCL13 in vitro while Th1 and Th2 have not this function.Then the relation between Th17 and CXCL13 needs further researches. to find out a model of EAMG that with a high success rate of establish.To find out the role of IL-17 and CXCL-13 in pathogenesis of MG.10-20 %of MG patients with thymoma,and 33-75% patients of thymoma with MG.70% patients of thymoma with MG Clinical symptoms improved or recovered after thymusectomy.So we consider that thymoma has a close relationship with myasthenia gravis. Still,the pathogenesis of thymoma with MG is sill not clear.Then to explore the probable roles of IL-17,CXCL-13 and CD4+T in pathogenesis of myasthenia gravis is very meaningful.In this study, rats with EAMG and 27 cases of thymoma patients as the research object,to explore the relationship between dose of H37 RA and pathogenesis of EAMG.The expression and relevance of IL-17 and CXCL13 in patients of thymoma with MG.Provide new targets for clinical treatment.Methods1.The role of H37 Ra in EAMG:Establish EAMG by hypodermic injection with peptide Complete Freund’s adjuvant(CFA),and H37 Ra. Then observe the rats by double-blind method for symptoms of EAMG once daily after injection.The weight of rat is observed at the same time.2.The role of TH17 and CXCL13 in EAMG: Establish EAMG by hypodermic injection with peptide Complete Freund’s adjuvant(CFA),and H37 Ra.Intraperitoneal injection Anti-Mouse/Rat IL-17 A additional,Test the level of CXCL13 in spleen, lymph gland and blood serum of rat.And test the level of lymph gland Ig G1, Ig G2 a,Ig G2 b.Compared with the ones with PBS.3.The role of IL-17 and CXCL-13 in pathogenesis of thymoma with MG:A retrospective analysis of thymoma for patients that after thymectomy.And immunohistochemical was conducted on thymoma tissues with antibodies to IL-17,CXCL-13 and CD4+.Then compares the two data results to find out the relationship between IL-17,CXCL-13 and thymoma with MG.4.Statistical analysis: Statistical analysis by SPSS 17.0.Differences between two groups were compared by t test.And P<0.05 is the level of significance.Results1.Two onset phase were 0bserved after injection region 97-116 of the rat acetylcholine receptor α subunit to lewis rats at the 7th and 35 th day after injection.EAMG incidence in rats improves to 75%,and with a higher myodynamia grade when plus the dose of H37 Ra.2.The level of CXCL13 in spleen, lymph gland and blood serum of EAMG rat has a significant rise. EAMG rats with IL-17 shows a more serious course of disease.The level of Ig G and Ig2 b is higher than the ones without IL-17.The groups with additional IL-17 has a higher level of CXCL13 in spleen, lymph gland and blood serum comparing to the ones without IL-17.3. B1,B2 and B3 type of thymoma has a higher probability at the same time with MG.The rate are 50%、60% and 66.7%.While C yupe of thymoma has a Little chance(0)with MG.Benign thymoma in more likely with MG and mainly type ⅡMG. Lymphocytic thymoma also has a high rate wihe MG. IL-17,CXCL13 and CD4+ cells have a higher positive rate in thymoma tumor tissues in patients with MG at the same time with thymoma.Conclusion1.Establish EAMG model with peptide fragment is a method that can be widely used.And H37 RA can greatly improve the success rate.2. IL-17 and CXCL13 play a important role in Pathogenesis of EAMG3.IL-17,CXCL13 and CD4+ cells were over-expressed in thymoma tumor tissues in patients with MG accompanied by thymoma.