| Objective:1.To analyze the expression of CD4+CD25+Foxp3+T cells in peripheral blood of patients with PM/DM,and to discuss its role in the pathogenesis of PM/DM.2.To explore the relationship between CD4+CD25+Foxp3+T cells and the clinical characteristics of PM/DM patients.3.To analyze the relationship between CD4+CD25+Foxp3+T cells and serological and immunological indexes of patients with PM/DM,and to discuss its significance in the diease activity evaluation of PM/DM.4.To analyze the relationship between CD4+CD25+Foxp3+T cells and the abnormalities of muscle MRI of PM/DM patients,and to explore the value of CD4+CD25+Foxp3+T cells combined with MRI in disease diagnosis and evaluation in PM/DM.5.To compare the changes of CD4+CD25+Foxp3+T cells in patients with PM/DM before and after treatment,and to explore its significance in the therapeutic evaluation.Methods:1.A total of 155 DM patients,29 PM patients and 193 healthy controls were enrolled.Clinical data including age,gender,duration and major clinical manifestations(organ involvement,such as lung,heart and digestive tract)of the patients were recorded in detail.Laboratory results of patients and healthy controls were recorded,including ESR,CRP,CK,CKMB,LDH,HBDH.The percentages and absolute counts oflymphocyte subsets and CD4+T cell subsets in peripheral blood of patients and healthy controls were determined by flow cytometry.2.The levels of cytokines IL-2,IL-4,IL-6,IL-10,INF-γ,IL-17 A and TNF-α in peripheral blood of 35 patients with PM/DM and 30 healthy controls were detected by Cytometric Beads Array(CBA).ANA of 159 patients and myositis antibody spectrum of140 patients were detected.3.Magnetic resonance imaging(MRI)of bilateral thigh muscles was performed in65 patients with PM/DM.T1/T2-weighted and short tau inversion recovery(STIR)fat-suppressed T2-weighted imaging were performed with fast spin echo(FSE)sequences.Fat imaging was performed with the GRE sequence.4.53 patients with PM/DM were categorized into two groups.Twenty six patients received conventional treatment(glucocorticoid + DMARDs),and 27 patients received low-dose IL-2 treatment on the basis of conventional treatment.The patients were followed up at 0W,1W,and 12 W of treatment and serological and immunological indicators were detected.Results:1.Compared with healthy controls,the percentages and absolute counts of CD4+CD25+Foxp3+T cells in peripheral blood of DM and PM patients were significantly lower(P < 0.001),and the Th17/Treg ratio were significantly increased(P <0.01).At the same time,the absolute numbers of total T,CD4+T,CD8+T,NK,Th1 and Th17 cells were significantly decreased.2.The levels of CD4+CD25+Foxp3+T cell in DM and PM were negatively correlated with disease duration,while Th17/Treg ratios were positively correlated with duration(P < 0.05).There was no correlation between CD4+CD25+Foxp3+T cells and gender or age in DM/PM patients.3.In PM/DM patients,the percentages and absolute numbers of CD4+CD25+Foxp3+T cells and Th1 cells in the organ-involvement group weresignificantly lower than those in the no organ-involvement group,though the Th17/Treg ratio were obviously higher(P < 0.05).4.The absolute counts of CD4+CD25+Foxp3+T cells in PM/DM were negatively correlated with the levels of ESR,CK,CKMB,LDH and HBDH(P < 0.05),and had no correlation with CRP.5.Compared with healthy controls,patients with PM/DM showed increased levels of INF-γ,IL-17 A,TNF-α,IL-4,and IL-10(P < 0.001),an increasing trend of IL-6,and no difference of IL-2 between the two groups.6.The absolute counts of CD4+CD25+Foxp3+T cells and Th2 cells in PM/DM patients with ANA positive were significantly lower than those in patients with ANA negative(P < 0.05).No significant difference existed in the absolute counts of CD4+CD25+Foxp3+T cells between the positive and negative groups of anti-Jo-1antibody,anti-Mi-2 antibody and anti-Ku antibody.7.Among the 65 PM/DM patients who undergoing muscle MRI examination,57 had abnormal muscle MRI,including muscle edema,myofascitis and fatty infiltration.Compared with PM/DM without fatty infiltration,the absolute counts of CD4+CD25+Foxp3+T cells reduced significantly while the ratio of Th17/Treg were increased significantly in PM/DM with fatty infiltration(P < 0.05).8.In PM/DM patients who receiving IL-2 treatment,the levels of ESR,CRP,CK,CKMB,LDH and HBDH decreased significantly at 1W and 12 W after treatment compared with those before treatment(P < 0.05),furthermore,CD4+CD25+Foxp3+T cells were continuously increased at the 1W and 12 W after treatment,while Th17/Treg ratios were decreased,respectively(P < 0.05).In PM/DM patients who receiving conventional treatment,the levels of ESR and CRP and the absolute counts of Treg cells were decreased significantly,and the Th17/Treg ratios were increased significantly at12 W after treatment compared with those before treatment,while muscle enzyme had no significant change.Conclusion:1.Patients with PM/DM had immune imbalance of Th17/Treg caused by reduction of CD4+CD25+Foxp3+T cells,which was partly involved in the pathogenesis of PM/DM.2.The absolute counts of CD4+CD25+Foxp3+T cells were negatively correlated with the levels of ESR and muscle enzyme in PM/DM patients,suggesting that these cells could be used as a reference index for disease evaluation.3.The absolute counts of CD4+CD25+Foxp3+T cells in the organ-involvement group were significantly lower than those in the no organ-involvement group,suggesting that the risk of organ involvement may increase with the decrease of CD4+CD25+Foxp3+T cells in the patients with PM/DM.4.The absolute counts of CD4+CD25+Foxp3+T cells were negatively correlated with fatty infiltration of muscle,suggesting that the reduction of these cells might be associated with chronic muscle injury,and these cells had some value in the evaluation of PM/DM muscle lesions.5.CD4+CD25+Foxp3+T cells can be used as one of the immune indicators to evaluate the efficacy of PM/DM.Immunoregulatory therapy is more suitable for patients with reduced CD4+CD25+Foxp3+T cells than immunosuppressive drugs. |
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