The Study Of The Role Of Regulatory T Cells And Th17 Cells And Th17/treg Balance In The Pathogenesis Of Dermatomyositis

Objective:To investigate the changes of the percentage of regulatory T cells and Th17cells in peripheral blood lymphocytes and the balance of Th17/Treg in patients with dermatomyositis(DM),and to study the possible role of Th17/Treg balance in development process of the disease of dermatomyositis,and to provide a theoretical basis to find a new target for the treatment of DM.Methods:In this study,we selected 46 cases of patients with dermatomyositis from outpatient or inpatient department of rheumatology department of Anhui Provincial Hospital from May 2016 to January 2018,all patients met the diagnostic criteria of Bohan/Peter in 1975.Among them,10 cases were DM-NILD,36 cases were DM-ILD.Divided into three groups according to disease course,there were 15 cases with disease course of<3 months,16 cases with 3 months?disease course<6 months,and 15 cases with disease course of?6 months.26 cases healthy controls were selected from our hospital healthy people during same period.Peripheral blood samples were collected from patients with dermatomyositis and healthy controls.After PBMCs were isolated,the frequency of CD4~+CD25~+Foxp3~+Treg cells and CD4~+IL-17~+Th17 cells in the peripheral blood of the patients and control group were detected by flow cytometry(FCM).To count Th17/Treg ratio,and to analyze its relationship with the clinical and laboratory indicators of DM.All data were statistically analyzed using the SPSS 16.0statistical software.Results:(1)About the Treg/CD4~+T cell:When grouped according to with or without ILD,the percentage of Treg cells in peripheral blood of healthy control group,DM-NILD group and DM-ILD group were 1.33±0.29(%),0.88±0.30(%),0.64±0.24(%),and the difference between the three groups was statistically significant(F=42.86,P<0.05).Further comparisons showed that the percentage of Treg cells in DM-NILD group and DM-ILD group were significantly lower than that in healthy control group(P<0.05).The levels of Treg cells in DM-ILD group was lower than that in DM-NILD group(P<0.05).When grouped according to disease course,the percentage of peripheral blood Treg cells in the<3 month group,3~<6 month group,and?6 month group was 0.64±0.16(%),0.68±0.25(%),and 0.67±0.27(%),respectively.The results were not statistically significant(F=0.136,P>0.05).Compared with the healthy control group,the percentage of Treg cells in patients with dermatomyositis of different stages was significantly lower(P<0.05).DM patients are divided into MDA5antibody-positive group and negative group according to the presence or absence of MDA5 antibody,The proportion of CD3~+CD4~+T lymphocytes in the positive group[27.15(19.35,36.00)%]was lower than the negative group[34.75(30.05,42.60)%],the difference between the two groups was statistically significant(Z=-1.993,P<0.05);The number of Treg cells in CD4+T lymphocytes was decreased,Treg cells in positive group[0.60(0.52,0.81)%]were significantly lower than those in negative group[0.79(0.61,1.11)%],but the difference was not statistically significant(P>0.05).According to the prognosis of the patients,they were divided into the death group and the better group,the proportion of Treg cells in the death group[0.51±0.11(%)]was significantly lower than that in the better group[1.02±0.82(%)],the difference between the two groups was statistically significant(t=-3.473,P<0.05).(2)About the Th17/CD4~+T cell:When grouped according to with or without ILD,the percentage of Th17 cells in peripheral blood of healthy control group,DM-NILD group and DM-ILD group were 1.27±0.43(%),2.08±0.24(%),2.82.±0.94(%),the difference between the three groups was statistically significant(F=29.37,P<0.05).Further comparisons showed that the percentage of Th17 cells in DM-NILD group and DM-ILD group were significantly higher than that in healthy control group(P<0.05).The levels of Th17 cells in DM-ILD group were higher than that in DM-NILD group(P<0.05).When grouped according to disease course,the percentage of Th17 cells in peripheral blood in the<3 month group,3~<6 month group,and?6 month group was2.38±0.76(%),2.87±1.13(%),and 2.62±0.83(%),respectively.The results were not statistically significant(F=1.051,P>0.05).Compared with the healthy control group,the percentage of Th17 cells in patients with dermatomyositis of different stages was significantly higher(P<0.05).(3)The ratio of Th17/Treg:When grouped according to with or without ILD,the Th17/Treg ratio in healthy control group,DM-NILD group and DM-ILD group were1.00±0.26,2.52±1.15 and 5.24±3.36,the difference between the three groups was statistically significant(F=18.77,P<0.05).Further comparisons showed that the Th17/Treg ratio in DM-NILD group and DM-ILD group were higher than that in healthy control group,and the Th17/Treg ratio in DM-ILD group was higher than DM-NILD group,the differences were statistically significant(P<0.05).When grouped according to disease course,the ratios of Th17/Treg in the<3 month group,<6 month group,and?6 month group were 3.94±1.60,5.10±3.59,5.07±3.86,respectively,and the results were statistically significant(F=9.52,P<0.05),compared with the<3 months group,the Th17/Treg ratio in the 3 to<6 months group and?6 months group was significantly higher;Compared with the healthy control group,the Th17/Treg ratio in patients with dermatomyositis of different stages was significantly higher(P<0.05).(4)Correlation analysis of Th17,Treg,Th17/Treg and laboratory indicators:Treg cells in DM-ILD group had no correlation with AST,ALT,CK,LDH,CRP and ESR,Th17was positively correlated with ESR(R=0.396,P<0.05),but had no correlation with AST,ALT,CK,LDH and CRP.The ratio of Th17/Treg was positively correlated with ESR(r=0.341,P<0.05),but had no correlation with AST,ALT,CK,LDH and CRP.The Treg,Th17,Th17/Treg in DM-NILD group had no correlation with AST,ALT,CK,LDH,CRP and ESR.Conclusions:The decrease in Treg cells,increase in Th17 cells,and disruption of Th17/Treg balance may be involved in the pathogenesis of dermatomyositis and is associated with interstitial lung disease.The decrease of Treg cells is related to the positive of MDA5 antibody.The fewer Treg cells,the worse the prognosis of patients with dermatomyositis.