免疫性血小板减少症Th1和Th2趋化因子及其受体表达的研究

The expression of Th1/Th2-associated chemokines and their receptors in patients with immune thrombocytopenia

目的免疫性血小板减少症(immune thrombocytopenia,ITP)是一种获得性自我免疫紊乱导致的出血性疾病,本文旨在研究ITP患者体内T-helper 1(Th1)趋化因子CCL5、CXCL11及其受体CCR5、CXCR3和Th2趋化因子CCL11及其受体CCR3的表达变化,以探讨趋化因子及其受体在ITP免疫异常中的作用。方法选择28名活动性ITP患者为研究对象,随机选取21名与ITP患者相匹配的健康人作对照组。以酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测ITP患者和对照组血浆中CCL5、CXCL11和CCL11的含量,采用实时聚合酶链式反应(real-time polymerase chain reaction,RT-PCR)检测外周血单个核细胞(PBMC)CCL5、CXCL11、CCL11、CCR5、CXCR3以及CCR3 mRNA的表达。结果 Th1相关趋化因子CCL5和Th2相关趋化因子CCL11在活动性ITP患者血浆中含量均低于正常对照组(P<0.05),而Th1趋化因子CXCL11升高(P<0.05);ITP患者PBMC的CXCL11 mRNA表达高于对照组,CCL11 mRNA表达低于对照组(P<0.05),而CCL5 mRNA在ITP组与对照组差异无显著性(P>0.05)。ITP患者血浆中Th1相关趋化因子受体CCR5和CXCR3表达量高于对照组(P<0.05),Th2相关趋化因子受体CCR3降低(P<0.05)。经过糖皮质激素等治疗有效的22例患者,Th1趋化因子CXCL11、趋化因子受体CCR5和CXCR3均下降(P<0.05),血浆CCL5含量回升,但是仍低于对照组(P<0.05);而Th2相关趋化因子CCL11及其受体CCR3均回升(P<0.05)。结论 Th1/Th2相关趋化因子及其受体的异常表达可能参与了ITP的免疫紊乱,是ITP发病因素之一;阻断Th1相关趋化因子与其受体的作用途径,可望成为ITP的生物调控靶点。

Immune thrombocytopenia（ITP） is an acquired autoimmune disorder with low platelet count and significant bleeding. In this study, to investigate the role of chemokines and their receptors in pathogenic process of ITP, we detected the expression of Th1-associated chemokines（CCL5 and CXCL11） and Th2-associated chemokines（CCL11） as well as their corresponding receptors CCR5, CXCR3 and CCR3 on peripheral blood mononuclear cells（PBMCs） of active ITP patients. Enzyme-linked immunosorbent assay（ELISA） was employed to measure the concentration of CCL5, CXCL11 and CCL11 in plasma samples from 28 patients with ITP and 21normal healthy subjects. The mRNA levels of CCL5, CXCL11, CCL11, CCR5, CXCR3 and CCR3 on PBMCs were determined by real-time polymerase chain reaction（RT-PCR）. We found that the levels of CCL5 and CCL11 in plasma were lower in ITP patients than those in healthy control, but CXCL11 level was higher than that in control（P 0.05, respectively）. The gene expressions of CCL11 and CXCL11 on PBMCs respectively showed similar results to their protein expression in plasma, while the gene expression of CCL5 showed no statistical significance between ITP and control groups. The expression levels of Th1-associated receptors CCR5 and CXCR3 were higher in ITP patients than those in healthy control（P 0.05）. However, the expression of Th2-associatedreceptor CCR3 exhibited an opposite result. More importantly, the expression of Th2-associated chemokine CCL11 and its receptor CCR3 in the effectual group with glucocorticoids management were up-regulated. Meanwhile, the Th1-associated chemokine CXCL11 and the receptors CCR5/CXCR3 were down-regulated. From all the results, we get a conclusion that the imbalanced expression of Th1/Th2 chemokines and chemokine receptors might play an immune pathogenic role in ITP. And interfering Th1 chemokine-chemokine receptor signaling might be effective in the treatment of ITP.