胆汁中趋化因子IP-10及其可溶性受体CXCR3与移植肝急性排斥反应的相关性

目的:观察胆汁中趋化因子IP-10及其可溶性受体CXCR3(sCXCR3)的动态变化,探讨其与移植肝急性排斥反应(AR)的关系。方法:以2007年10月～2008年3月在本院行肝移植术的28例患者为研究对象,按急性排斥反应发生与否分为AR组(n=8)和NAR组(n=20)；另选本院消化科因胆石症行鼻胆管引流(ENBD)的患者10例作为对照。采用双抗体夹心ELISA方法检测患者移植术后第1、3、5、7天和激素冲击治疗第1、3、7天胆汁中趋化因子IP-10及sCXCR3的表达变化,分析其与肝穿刺活检Banff排斥活动指数(RAI)的相关性,评价其对AR的诊断价值。结果:肝移植患者术后胆汁中趋化因子IP-10及sCXCR3的表达水平逐渐升高,术后第5天达到高峰,且从第5天开始,AR组患者的表达水平显著高于NAR组和ENBD组(P<0.05)；经激素冲击治疗后,IP-10及sCXCR3的表达水平明显下降(P<0.05)。AR确诊当日,胆汁中趋化因子IP-10及sCXCR3的表达水平与RAI具有良好相关性(P<0.05)。术后第5天,截断值为964.45 pg/ml时,IP-10诊断AR的敏感性为87.5%,特异度为100%；术后第7天,截断值为819.35 pg/ml时,sCXCR3诊断AR的敏感性为87.5%,特异度为80%。结论:肝移植术后早期,胆汁中趋化因子IP-10及sCXCR3的动态变化与移植肝急性排斥反应密切相关,有望成为AR早期诊断及抗排斥治疗效果的无创监测指标。

Relationship of chemokine IP-10 and its soluble CXCR3 in bile with acute graft rejection after liver transplantation

Objective:To observe the dynamic changes of chemokine IP-10 and its soluble receptor CXCR3 in bile,and to explore its relationship with acute graft rejection (AR) after liver transplantation.Methods: A total of 28 patients who underwent orthotopic liver transplantation in our hospital between October 2007 and March 2008 were included in the present study.They were divided into 2 groups according to the presence of AR: AR(n=8) and NAR(n=20).Another 10 patients who underwent endoscopic nasobiliary drainage (ENBD) for cholelithiasis in our hospital served as controls.The levels of chemokine IP-10 and sCXCR3 in the bile were determined by ELISA assay on 1,3,5,and 7 days after transplantation in all the patients and on 1,3,and 7 days after the anti-rejection therapy with glucocorticoid in patients of AR group; the relationship between their levels and the rejection active index (RAI) obtained by Banff criteria were evaluated; and its diagnostic value for AR was assessed.Results: The levels of IP-10 and sCXCR3 in bile gradually increased after liver transplantation and reached the peak on the 5th day after transplantation,and starting from day 5 after transplantation,their levels were significantly higher in the AR group than in the NAR group and ENBD group (P<0.05).Besides,the levels of IP-10 and sCXCR3 in bile were significantly decreased after treatment with glucocorticoid (P<0.05).On the day of AR diagnosis,the the levels of IP-10 and sCXCR3 in bile were significantly correlated with RAI (P<0.05).On the 5th day after transplantation,the diagnostic sensitivity and specificity of IP-10 level for AR were 87.5% and 100%,respectively (cut-off point=964.45 pg/ml); on the 7th day after transplantation,the diagnostic sensitivity and specificity of sCXCR3 were 87.5% and 80%,respectively (cut-off point=819.35 pg/ml).Conclusion: The levels of IP-10 and sCXCR3 in bile are closed related with early graft acute rejection,and their levels may serve as a non-invasive diagnostic indicator for AR and outcome of anti-rejection therapy.