The Change Of Peripheral Blood T Cell Subsets And The Influence Of Rapamycin On Th17/Treg Balance In Patients With Primary Sjogren's Syndrome

Objective:1.To analyze the changes of lymphocyte subsets and CD4~+T cell subsets in peripheral blood of patients with PSS;2.To investigate the correlation between lymphocyte subsets,CD4~+T lymphocyte subsets and ESR,ESSDAI in patients with PSS;3.To explore the influence of rapamycin on the absolute number of Th17,Treg cells,Th17/Treg,ESR and ESSDAI in patients with PSS.Methods:A total of 79 PSS patients were included,including 5 males and 74 females.All of them met the 2002 PSS International Classification Standard and excluded other autoimmune diseases,hematologic diseases,graft-versus-host disease(GVHD),and malignant tumors.They are outpatients and inpatients with PSS from the Department of Rheumatology,the second hospital of shanxi medical university from March 2016 to October 2017.At the same time,30 cases doctors and nurses in our hospital as a healthy control group were included,who matched the gender and age with PSS patients,without clinical symptoms of autoimmune diseases.79 cases of PSS patients were divided into group A(20 cases)and group B(59 cases),in which group A were newly diagnosed patient,without traditional treatment,group B was treated with conventional therapies including glucocorticoids(GCs)and disease modifying antirheumatic drugs(leflunomide,hydroxychloroquine,methotrexate,cyclophosphamide)in the past 6 months.Among the79 cases patients with PSS,45 cases were given Rapamycin(RAPA)combined with conventional therapy,RAPA 0.5mg/day,once every other day,including 12 cases of group A(with RAPA and traditional treatment)and 33 cases group B(based on the original treatment plus RAPA).The gender,age and general clinical manifestations of all the subjects were collected,and the disease activity score was assessed by EULAR-SS Disease Activity Index(ESSDAI).Peripheral blood was collected from all subjects.Flow cytometry was used to detect lymphocyte subsets and CD4+T cell subsets.PSS patients were with conventional laboratory tests at the same time and PSS patients who were added with RAPA were respectively detected and analyzed lymphocyte subsets and CD4+T cell subsets after RAPA 12 weeks and 24 weeks.All the data were analyzed by SPSS 20.0.Results:1.Compared with the healthy control group,the absolute number of NK,Th1,and Treg cells in the PSS group were decreased(P<0.05),and the absolute cell number of Th2 and Th17 were increased(P<0.05).Th1/Th2 was significantly decreased,Th17/Treg was significantly increased(P<0.001).The absolute number of T,B,CD4~+T,CD8~+T,T+B+NK cells and CD4~+T/CD8~+T between two groups were not statistically significant(P>0.05).2.The absolute number of Treg cells in PSS patients were negatively correlated with ESSDAI scores(r=-0.366,P<0.05),Th17/Treg were positively correlated with ESSDAI scores(r=0.358,P<0.05),but the absolute number of T,B,CD4~+T,CD8~+T,NK,Th1,Th2,Th17 cells,CD4~+T/CD8~+T and Th1/Th2 had no correlation with ESSDAI.At the same time the lymphocyte subsets had no correlation with ESR;3.There was no significant difference in absolute number of Th17,Treg cells,and Th17/Treg between group A and group B(P>0.05);4.Compared with the healthy control group,the absolute number of Th17 cells in group A increased(P<0.05),Th17/Treg increased(P<0.01),the absolute number of Treg showed a decreasing trend(P>0.05);in group B,the absolute number of Treg cells decreased(P<0.01),the absolute number of Th17 cells increased(P<0.05),Th17/Treg increased(P<0.001);5.Compared with pre-RAPA PSS group,after RAPA treating 12 weeks,the absolute number of Th17,Treg cells and Th17/Treg were not statistically significant(P>0.05),and after RAPA treating 24 weeks,the absolute number of Th17 cells and Th17/Treg were decreased(P<0.01),the absolute number of Treg cells were increased(P<0.05);compared with the healthy control group,in the PSS group before RAPA treatment,the absolute number of Th17 cells were increased(P<0.05),Th17/Treg were increased(P<0.001),the absolute number of Treg cells were decreased(P<0.01),after RAPA treating for 12 weeks,the absolute number of Th17 cells were increased(P<0.05),Th17/Treg were increased(P<0.01),the absolute number of Treg cells was not statistically significant(P>0.05),but after RAPA treating for 24 weeks,the absolute number of Th17,Treg cells and Th17/Treg was not statistically significant(P>0.05);6.Compared with pre-RAPA PSS group,there was no significant change in ESR after12 and 24 weeks of RAPA treatment;the ESDAI score showed a decreasing trenda,and the difference was not statistically significant.Conclusion:1.Peripheral blood T cell subsets of patients with PSS were abnormal,among which the absolute number of Treg cells decreasing,led to the imbalance of Th17/Treg and may be an important factor in its pathogenesis;2.Rapamycin can promote the differentiation of Treg cells,inhibit the production of Th17 cells,induce the recovery of the Th17/Treg,may reduce the disease activity,and require long-term maintenance treatment.