Effects Of Circulating T Helper Cells On Myasthenia Gravis

Objective:To investigate the function of various types of Th cells in the pathogenesis of MG. Methods:Thirty-three MG patients, admitted to the Department of Neurology, the First Hospital of Jilin University, from 2015.1 to 2015.12, were enrolled in our study. Blood samples of them were collected, and the quantitative myasthenia gravis score(QMGs) were used to evaluate the severity of the disease. Osserman clinical classification was finished according to the scope of skeletal muscle involvement and the severity of the disease. The proportion of Tfh cells in peripheral blood obtained from MG patients and healthy controls were measured by flow cytometry. The concentration of serum IL-17 A, IFN-γ, IL-4 and IL-21 were detected by cell based assay(CBA), while the level of serum IL-22 were detected by ELISA. Results:1.The frequency of Tfh cells(CXCR5+CD4+ T 、 CD45RO+CXCR5+CD4+ T 、ICOS+CXCR5+CD4+ T and PD-1+CXCR5+CD4+ T) obtained from MG patients was significantly upregulated when compared to healthy controls(P=0.040, P=0.018, P=0.035, P<0.001).2. The expression of IL-21, IL-17 A and IFN-γ was significantly elevated compared to healthy controls(P=0.047, P=0.023, P=0.028).3. The expression of IL-4 of type IIa MG patients was significantly upregulated when compared to type IIb and III MG patients(P=0.028,P=0.044).4. The frequency of Tfh and the expression of IL-4, IL-17 A, IL-21, IFN-γ, IL-22 from MG patients with thymic hyperplasia and thymoma was no significant difference compared with that of MG with normal thymus(P>0.05).5. No significant difference of Tfh cells and the expression of IL-4, IL-17 A, IL-21, IFN-γ, IL-22 between myasthenia crisis group and no myasthenia crisis group was found. The ratio of IL-21/IL-4 in myasthenia crisis group was significantly elevated compared to no myasthenia crisis group(P=0.041).6. No correlations was found between Tfh and the expression of IL-4, IL-17 A, IL-21, IFN-γ, IL-22.7. The frequency of PD-1+CXCR5+CD4+ T cell was found to be correlated to QMGs(r=0.405, P=0.019).8. The expression of IL-4 was associated with QMGs(r=- 0.393, P=0.024). Conclusion:1. ICOS+ and PD-1+ circulating Tfh cells have positive immune regulation effects in the pathogenesis of myasthenia gravis.2. IL-17 A and IFN-γ has positive immune regulation effects in the pathogenesis of myasthenia gravis.3. IL-4 may have negative immune regulation effects in the pathogenesis of myasthenia gravis.