Effects Of Follicular Regulatory T Cells On Myasthenia Gravis

Objective:To investigate the effect of follicular regulatory T cells (Tfr) in the pathogenesis of myasthenia gravis(MG).Methods:The venous blood of MG patients were collected at xiangya hospital from2013to2014, and the clinical data was recorded in detail.According to the scope of skeletal muscle involvement and the severity of the disease, MGFA clinical classification and QMG score were finished.The frequency of Tfr,natural regulatory T cells (Treg) and follicular helper T cells (Tfh) in peripheral blood mononuclear cells (PBMCs) obtained from patients with MG and healthy controls were determined by flow cytometry. Investigate the relationship between Tfr and disease severity, clinical feature, immunotherapy.Resrults:(1)The frequency of Tfr and Treg in PBMCs obtained from patients with MG was significantly downregulated compared to heathy controls, as well as the Tfr/Treg ratio and the Tfr/Tfh ratio.But the expression of Tfh was significantly upregulated.(2) In generalized myasthenia gravis(GMG) group,the frequency of Tfr. and the Tfr/Treg ratio were significantly downregulated compared to ocular myasthenia gravis(OMG) group(P<0.05).But the frequency of Tfh and Treg was no significant difference between GMG and OMG group(P>0.05). The frequency of Tfr,Tfhand Treg in PBMCs from MG patients was no significant difference, according to MGFA classification.(3) The frequency of Tfr,Tfh,and Treg was no significantly correlated with age and gender(P>0.05). The frequency of Tfr of MG patients with less than one year duration was significantly upregulated, compared to others.The Tfr/Treg and Tfr/Tfh ratio was significantly reduced.(4)The frequency of Tfr,Tfh and Treg in PBMCs from MG patients with thymic hyperplasia and thymoma was no significant difference compared with that of MG with normal thymus.(5) In steroids therapy group,the frequency of Tfr and Treg was significantly upregulated compared to negative control group,while the frequency of Tfh was significantly downregulated (P<0.05). The frequency of Tfr and Treg was significantly increased after steroids therapy, while the frequency of Tfh was decreaseded.(6)The significant expression of Tfr, Treg and Tfh, as well as the ratio of Tfr/Treg and Tfr/Tfh was significantly relevant to QMG score.Correlation index of Tfr, Treg, Tfh, Tf/Treg and Tfr/Tfh were0.5450,-0.3840,0.4284,-0.3839and-0.6359,respectively.(7) The significant lower expression of Tfr was no significantly relevant to the expression of Tfh.But the percentage of Tfr was positively correlation with the level of Treg, in which correlation coefficient was0.4318(p<0.001).Conclusion:Follicular regulatory T cells has negative immune regulation effects in the pathogenesis of myasthenia gravis, which may be related to natural regulatory T cells or follicular helper T cells.