The Change Of Absolute Number Of Regulatory T Cells In Peripheral Blood Of Patients With Primary Sjogren's Syndrome And Short-time Effect Of Low Dose Of IL-2

Objective:To explore the change of the number of Th17 and Treg(CD4~+CD25~+Foxp3~+T cells)cells in peripheral blood in pSS and the effects of low dose IL-2 therapy on the balance of Treg and Th17 cells.Determine whether there is a difference of the absolute number of Treg cells in peripheral blood between patients with pSS and healthy controls.Elucidate the difference of the absolute number of CD4~+CD25~+T cells and CD4~+CD25~+Foxp3~+T cells,explore the difference of change of percentage and absolute number of cells and describe the difference of absolute number of lymphocyte subsets after using drugs including CTX(cyclophosphamide),MTX(Methotrexate),HCQ(hydroxychlorquine),and LEF(Leflunomide).Methods:One hundred and ninety pSS patients in our department,and 30 healthy controls were put in the research.The amount of Th17 cells and Treg cells were calculated by flow cytometry.Eighty eight in 192 were given low-dose IL-2(5*10~6 IU/day for 5 days)by hypodermic injection combined with standard therapy which includes glucocorticoid,immune-suppressants,biological agents or combination of them,while others(12 in 69)were given standard therapy only.The amount of these cells were calculated again after therapy.The Kruskal-Wallis test was used to compare the absolute number of cells between newly diagnosed pSS patients,return visit pSS patients,and healthy controls.Paired two-tailed non-parametric tests will be used to compare the immunological characteristics of IL-2 before and after treatment.P<0.05 was considered statistically significant.Results:There was significant decrease in the absolute number of Treg cells and significant increase of the ratio of Th17/Treg cells in pSS patients when compared with healthy controls.There was no significant difference in absolute number of Th17 cells between pSS patients and healthy controls.Further,the number of Treg cells were negatively relative to ESSDAI.Traditional DMARDs had no obvious impact on Treg and Th17 cells.The amount of Treg cells significantly increased after the treatment of IL-2 by 1 week.But there was no significant improvement in clinical manifestations in the short time when comparing combinational treatment of IL-2 and classical drugs with classical therapy.No obvious adverse reactions were observed.To explore the long-term effects of low dose IL-2 on Treg cells,Th17 cells and the ratio of them in peripheral blood of Chinese Han patients with primary Sj?gren's syndrome.Conclusion:The number of CD4~+CD25~+Foxp3~+T cells in peripheral blood was decreased obviously and was inversely related to ESSDAI.While there was no significant difference of Th17cells between pSS patients and healthy controls.And there was no correlation between the number of Th17 cells and ESSDAI.So the imbalance of Th17/Treg is due to the decrease of Treg cells not increase of Th17 cell which indicates that the pathogenesis of pSS maybe mainly because of shortage of autoimmune tolerance.Low dose IL-2 therapy can effectively promote proliferation of Treg cells by which low dose IL-2 may induce and restore autoimmune tolerance to benefit disease control.