髓系来源抑制细胞与类风湿关节炎炎性因子的相关性研究

Study on the correlation between myeloid source inhibition cells and rheumatoid arthritis factors of rheumatic immune

目的观察髓系来源抑制细胞(MDSC_s)与类风湿关节炎炎性因子的相关性。方法回顾性纳入于2015年8月至2017年8月收治的58例类风湿关节炎患者为观察组,另选取同期收治的58例的健康体检者为对照组。采集两组空腹乙二胺四乙酸(EDTA)抗凝血2~3 ml。采用流式细胞术与RT-q PCR检测信号转导与转录活化因子3(STAT3)、人白细胞介素-17A(IL-17A)mRNA表达水平,并经酶联免疫吸附实验(ELISA)测定两组血浆中人白细胞介素-1β(IL-1β)、人白细胞介素-6(IL-6)、人白细胞介素-10(IL-10)、IL-17A细胞因子。观察类风湿关节炎患者外周血中MDSCs表达量。按照DAS28评分评估类风湿关节炎疾病活动,将观察组分为缓解期组、活动期组,比较缓解期组、活动期组与对照组MDSCs、红细胞沉降率(ESR)、C反应蛋白(CRP)、DAS28评分,分析MDSCs表达量与炎症细胞因子的关联性。结果观察组外周血中MDSCs的表达水平为(6.20±4.21)%,高于对照组(1.60±1.21)%,差异有统计学意义(P<0.05)。缓解期组MDSCs表达水平与ESR水平显著低于活动期组(P<0.05),且显著高于对照组(P<0.05);缓解期组CRP水平显著低于活动期组(P<0.05),较对照组差异无统计学意义(P>0.05),且DAS28评分显著低于活动期组(P<0.05)。MDSCs百分率增加与疾病活动、ESR呈正相关(P<0.05),与CRP无相关性(P>0.05)。观察组细胞因子IL-1β、IL-6、IL-10、IL-17A水平显著高于对照组(P<0.05),PBMCs中IL-17A、STAT3mRNA的表达水平较对照组差异无统计学意义(P>0.05)。通过Spearman相关性分析,发现类风湿关节炎患者PBMCs中MDSCs数量与STAT3 mRNA表达水平呈负相关(P<0.05),与细胞因子IL-1β、IL-10表达水平呈正相关(P<0.05),与IL-6、IL-17A表达水平无相关性(P>0.05)。结论类风湿关节炎患者外周血中MDSCs数量明显上升,与疾病严重程度相关,其表达量为炎症反应活动的关键指标。

Objective To observe the correlation between Myeloid-derived suppressor cells （MDSCs） and rheumatoid arthritis factors of rheumatic immune system. Methods 58 cases of rheumatic arthritis patients were enrolled from August 2015 to August 2017 as the observation group, were selected 58 cases of healthy control group from our hospital, were collected fasting EDTA anticoagulant 2~3 ml. The expression of signal transduction and transcription activator 3 （STAT3）, human interleukin-17A （IL-17A） mRNA was detected by flow cytometry RT-qPCR.The levels of plasma human interleukin-1 beta （IL-1 beta）, human interleukin-6 （IL-6）, human interleukin-10 （IL-10） and IL-17A in two groups was determined by ELISA.The amount of MDSCs expression in autoimmune rheumatic arthritis in the peripheral blood of patients with observation. The rheumatic arthritis disease activity was evaluated according to DAS28. The observation group was divided into remission group, activity group, comparison group, remission stage group and control group. MDSCs, ESR, CRP, DAS28 score, MDSCs expression analysis were compared with inflammatory cytokines. Results The expression level of MDSCs in the peripheral blood of the observation group was （6.20±4.21）%, and the control group was （1.60±1.21）%, and the difference was statistically significant （ P 〈0.05）. The CRP of remission group was significantly lower than that of the active phase group （ P 〈0.05）. There had no statistical significance compared with the control group （ P 〉0.05）, and the DAS28 score was significantly lower than that of the active phase group （ P 〈0.05）, confirmed that MDSCs increased the percentage of positively correlated with disease activity and ESR （ P 〈0.05）, No. with CRP （ P 〉0.05）. The levels of cytokines IL-1 beta, IL-6, IL-10 and IL-17A in the observation group were significantly higher than those in the control group （ P 〈0.05）, and the expression level of IL-17A and STAT3 mRNA in PBMCs did not have statistically significant compared with that in the control group （ P 〉0.05）. By Spearman correlation analysis, the study found that MDSCs rheumatic arthritis patients and the number of PBMCs in STAT3 mRNA expression was negatively correlated （ P 〈0.05）, positively correlated with cell factor IL-1 beta and IL-10 expression （ P 〈0.05）, and IL-6, IL-17A expression level has no correlation （ P 〉0.05）. Conclusion The number of MDSCs in patients with rheumatoid arthritis is obviously increased, which is related to the severity of the disease, and its expression is the key index of the activity of inflammatory reaction.