The Levels Of Serum Resistin And Its Relationship With Abnormal Differentiation Of CD4~+ Helper T Cell Subsets In Patients With Myasthenia Gravis

ObjectiveMyasthenia gravis(MG)is an antibody-mediated autoimmune inflammatory disease of the neuromuscular junction.It is mainly caused by the production of autoantibodies against muscle nicotinic acetylcholine receptor(AChR).The abnormal differentiation of CD4~+helper T cell subsets plays a key role in the pathogenesis of myasthenia gravis(MG).Recently,it has been identified that increased levels of resistin,a proinflammatory cytokine,can induce secretion of various cytokines via different inflammatory signaling pathways,and is involved in the pathogenesis of various autoimmune diseases,but its role and mechanisms in the pathogenesis of MG are still unclear.This study aims to explore the serum levels of resistin and its relationship with abnormal differentiation of CD4~+helper T cell subsets in MG patients.MethodsWe enrolled 79 MG patients with anti-AChR antibody positive and 32 healthy sex-and age-matched controls.The clinical data of patients were obtained from the MG database of the study group.The serum samples of MG with anti-AChR antibody positive were collected,and the levels of resistin were detected using a human resistin enzymelinked immunosorbent assay(ELISA)kit,and correlation with the severity of the disease was also analyzed.Moreover,CD4~+helper T cells were selected using magnetic bead separation method from blood samples of 15 newly hospitalized MG patients with anti-AChR antibody positive,and then divided into two groups:control group and intervention group of resistin(100ng/ml).The effect of resistin on the abnormal differentiation of CD4~+helper T cells was observed by flow cytometry.Results1.Compared with control subjects,the serum resistin levels of MG patients with anti-AChR antibody positive were significantly higher(P<0.001);When we compared resistin levels among different MG subtypes,patients with generalized MG(GMG)had significantly higher resistin levels than patients with ocular MG(P<0.001)and controls(P<0.001),but there was no significant difference between patients with ocular MG and control subjects(P>0.05);3.The relationship between serum resistin levels and MG-ADL scores in generalized MG patients with AChR antibody positive was analyzed.The result showed a positive correlation between serum resistin levels and MG-ADL scores in AChR-GMG-positive cases(r=0.424,P<0.01);4.In vitro,the serum resistin level MG untreated patients caused an increase in Th1/Th2 ratio,but there was no significant difference(r=0.382,P>0.05);after treatment of CD4~+helper T cells with 100ng/ml resistin,the Th1/Th2 ratio was significantly higher than that in controls(P<0.05).Conclusion1.The levels of serum resistin were significantly increased in GMG patients with anti-AChR antibody positive,and were positively correlated with the severity of the disease,suggesting that resistin may be involved in the autoimmune responses underlying MG;2.The ratio of Th1/Th2 was increased after treatment of CD4~+helper T cells with resistin,suggesting that resistin may be involved in the pathogenesis and immunoregulation of MG through the abnormal differentiation of CD4~+helper T cell subsets.