目的:本次研究通过检测类风湿关节炎(RA)患者外周血单核细胞亚群比例及其分泌促炎细胞因子的功能,探讨单核细胞亚群在RA发病过程中的作用。方法:22例RA患者(RA组)和22例健康对照者(HC组),经知情同意后抽取3ml静脉血,肝素钠抗凝。流式细胞术(FCM)检测单核细胞亚群比例、中间型单核细胞表面HLA-DR、Toll样受体2(TLR2)和髓系细胞触发受体-1(TREM-1)表达,及其细胞内肿瘤坏死因子(TNF)-α平均荧光强度(MFI),并分析RA患者单核细胞亚群比例与血清细胞因子的相关性。正态数据分析采用Students't-test检验。结果:与HC组相比,RA组中间型单核细胞比例升高[(4.6±1.2)%vs(11.7±1.6)%],差异有统计学意义(P〈0.05);HLA-DR表达(MFI)与HC组比较差异无统计学意义(26.8±8.6 vs 30.2±6.1,P〉0.05)。RA组TLR2(750.2±110.3 vs 526.8±98.6)、TREM-1(58.4±12.1 vs 40.3±10.2)表达(MFI)高于HC组,差异均有统计学意义(P〈0.05);RA组中间型单核细胞胞内TNF-α(46.3±6.4 vs 36.7±8.3)MFI高于HC组,差异有统计学意义(P〈0.05)。RA患者中间型单核细胞比例与DAS28评分和血清TNF-α、白细胞介素(IL)-17呈正相关,相关系数分别为0.593(P=0.003)、0.471(P=0.027)和0.538(P=0.009)。结论:RA患者外周血单核细胞向中间型极化,并处于活化状态,高表达TLR2和TREM-1,分泌较多的促炎细胞因子TNF-α,参与RA的疾病过程。因此,抑制单核细胞向中间型极化或阻断表面受体表达可能是治疗RA的新途径。
Objective: To explore the role of peripheral blood monocyte subsets in the pathogenesis of rheumatoid arthritis( RA),we therefore decided to compare the percentage of monocyte subpopulations in peripheral blood,as well as cytokines secretion function,to that of healthy controls. Methods: 22 patients with RA and 22 cases of healthy controls( HC) were drew 3 ml fresh venous blood into a tube containing heparin. The percentage of monocyte subsets,expression of Toll-like receptor( TLR) 2,HLA-DR,triggering receptor expressed on myeloid cells-1( TREM-1) on intermediate monocyte and mean fluorescence intensity( MFI) of intracellular tumor necrosis factor-α( TNF-α) were evaluated with the methods of flow cytometry( FCM). The correlation between percentage of monocyte subsets and serum cytokines was explored. Statistical significance between parametric data was determined by the students' ttest. Results: Compared to HC controls,the percentages of intermediate monocytes were significant higher in RA patients [( 11. 7 ±1. 6) % vs( 4. 6±1. 2) %,P〈0. 05],as well as the expression( MFI) of TLR2( 750. 2±110. 3 vs 526. 8±98. 6) and TREM-1( 58. 4±12. 1 vs 40. 3±10. 2) on intermediate monocytes( P〈0. 05). The expression of HLA-DR on intermediate monocytes of RA patients had no difference with HC controls( P〉0. 05),while MFI of intracellular TNF-α in intermediate monocytes of RA patients were significant higher than that of HC controls( 46. 3±6. 4 vs 36. 7±8. 3,P〈0. 05). In addition,RA patients showed a positive correlation between the percentage of CD14~(high)CD16~+monocytes and DAS28 scores( r = 0. 538,P = 0. 009),as well as the serum levels of TNF-α,IL-17( r =0. 471,P = 0. 027; r = 0. 593,P = 0. 003). Conclusion: Monocyte subpopulations from RA patients are abnormally skewed toward to intermediate monocytes which has high expression of TLR2,TREM-1 and the function of TNF-α secretion. Therefore,intermediate monocytes may play