The Role Of Th17 And Treg Cells In The Pathogenesis Of Polymyositis

Objective:1.To observe the each proportion of Th17 cells and Tregs cells with CD4+ T cells in peripheral blood of polymyositis patients, and the change of Th17/Treg immune balance in polymyositis, to explore the relationship between polymyositis and Th17/ Treg disturbances;2. To observe the trend of Th17 and Tregs cells proportion after treatment with glucocorticoids, to investigate the effect of glucocorticoid treatment on Th17/Treg balance, to explore the therapeutic value of correct Th17 cells and Treg cells immune disturbaces for polymyositis.3. To observe the expression of RORyt mRNA and Foxp3 mRNA in muscle tissue of patients with polymyositis, and further explore what is the role of Th17/Treg imbalance played in the immune pathogenesis of polymyositis.Methods:1.58 cases were enrolled in this study, divided into four groups,21 cases were polymyositis,10 cases were dermatomyositis,10 cases were limb girdle muscular dystrophy type 2B (LGMD2B) and 17 cases were healthy controls.The first three groups were confirmed by methods of muscle enzymohistochemistry and immunohistochemistry to fufill the criteria of respective diagnosis, other muscle diseases were ruled out. All patients’detailed clinical data were collected, including the primary clinical symptoms and signs, previous medicications used, serum muscle enzymes spectrum, EMG results, CT and MRI and other imaging findings, etc.2. ①Peripheral blood was obtained from polymyositis group (n=21) and healthy control group(n=17). Each proportion of Th17 cells and Tregs cells in CD4+T cells were detected by flow cytometry. The percentage of Th17 cells and Treg cells in the the peripheral blood mononuclear cells (PBMCs) were respective statistical compared between polymyositis group and healthy control group;②Polymyositis patients were divided into two groups by EMG results:active group (n=11) and stable group (n=10).The percentage of Th17 cells and Treg cells were respective statistical compared between the two groups;(3)In total 21 patients with polymyositis, there were 3 cases whom were new onset and first timetreatment.The variation trend of Th17 cells and Treg cells proportion were counted respectively when the three polymyositis cases received glucocorticoid therapy.3. Polymyositis cases(n=10) as the research group, dermatomyositis patients (n=10) and limb girdle muscular dystrophy type 2B(LGMD2B) (n=10)as the control groups, RORyt mRNA and Foxp3 mRNA expression of muscle tissue were measured by RT-PCR, the difference between polymyositis group and the two control groups was counted respectively,using SPSS 17.0 for statistical analysis.Results:1. Among 21 polymyositis cases,8 cases (38.1%) were male and 13 cases (61.9%) were female. The main clinical features were described as follow:weakness of limb-girdle muscle (100%);7 patients with neck weakness and 2 patients with sore muscle weakness; 8 patients had myalgia, proximal muscular atrophy wrer not obvious in all patients. The average CK value of 21 patients was 3240.79±3139.89 IU/L,and the average LDH value was 676.01±373.83IU/L U/L. The primary pathological changes showed a lot of inflammatory cells infiltration around necrotic muscle fibers.10 dermatomyositis patients all showed rash and symmetrical proximal limb girdle muscular weakness, the average CK value of 21 patients was 3035.66±3032.48 IU/L,and the average LDH value was 533.49±273.53IU/L.10 LGMD2B patients all showed weakness of limb girdle muscle, the average CK value of 21 patients was 6196.37±4968.39IU/L, and the average LDH value was 669.05±620.16IU/L.2.①Proportion of Th17 cell of PM group (1.21±0.35) was higher than that of healthy control (0.67±0.32) (p<0.0001), Treg cells were decreased in polymyositis patients (4.38±1.31) compared to healthy controls (6.13±1.54) (P=0.0006<0.05).②In the polymyositis patients, the Th17 cell population in active phase (1.36⒈0.33) was increased compared with levels in stable phase (1.03±0.25) (P=0.0138<0.05), while percentage of Tregs in active phase were decreased (4.18±1.33) compared to levels in in stable phase(4.62±1.32) (P=0.4313>0.05)③The proportion of Thl7cell trended towards a reduce after three patients of new onset were treated with glucocorticoids (0.9±0.1) compared with initial levels in the same three patients (1.43±0.12). In contrast, the proportion of Treg cells were increased in the three polymyositis patients after glucocorticoids treatment (4.00±0.61)compared with initial levels before treatment(2.93±0.15). Unfortunately, the number of cases is too small to make statistical comparisons.3. RORyt mRNA level of polymyositis group (1.06±0.10) was not higher than both of dermatomyositis control group (1.06±0.15) (p=0.48>0.05) and LGMD2B control group (0.89±0.05) (p=0.61> 0.05), the expression of Foxp3 mRNA in polymyositis group (1.19±0.29) was not markedly decreased compared with dermatomyositis control group (0.21±0.04) (p=0.07> 0.05)and LGMD2B control group (0.75±0.09 (p=0.19> 0.05).In a word,the difference was not statistically significant.Conclusions:1. Immune imbalance between Th17 cell and Treg cell may be related with polymyositis, and may contribute to the pathogenesis of PM indirectly.2.Strategies designed to regulate the function of Th17 cell and Treg cell tend to balance may be valuable approaches for the treatment of polymyositis.