肾移植亚临床排斥反应患者血清细胞因子水平变化及干预

Changes of serum cytokines and intervention in renal transplantation recipients with sub-clinical rejection

背景：肾移植后具有典型临床表现的急性排斥反应发生越来越少,但是受者长期服用免疫抑制剂的过程中,无明显临床症状,血肌肝上升不明显甚至正常的亚临床排斥反应现象频繁发生。目的：观察肾移植后亚临床排斥反应患者血清中白细胞介素2,6,8,10水平变化和C-反应蛋白变化及相互关系。设计、时间及地点：对照观察实验,于2006-06/2007-10在中南大学湘雅二医院完成。对象：接受同种异体肾移植原发性肾小球肾炎患者68例,男51例,女17例,年龄21-60岁。随访时间至少1年。正常对照人群20名。方法：根据临床症状、实验室免疫生化指标、彩色多普勒超声检查及移植肾病理活检,将随访68例患者分为亚临床排斥组和无排斥组,观察无排斥组和亚临床排斥组干预治疗前后血清细胞因子及免疫学指标的变化。主要观察指标：采用酶联免疫吸附法检测血清白细胞介素2,6,8,10水平,采用免疫速率散射比浊法和IMMAGE全自动免仪疫分析仪检测C-反应蛋白水平。结果：肾移植后,随访期患者白细胞介素2,6,8,10结果均高于正常对照组。发生亚临床排斥反应时,白细胞介素6,8,10显著高于未发生排斥组（P〈0.01）。干预治疗后,白细胞介素2,6,8逐渐降低,呈规律性的降至基础水平,白细胞介素6,8与C-反应蛋白水平呈明显正相关（r=0.92,P〈0.01;r=0.85,P〈0.01）。白细胞介素10在发生排斥时激剧上升,然后下降,甚至出现一过性低于基础水平,干预治疗有效后逐渐上升至基础水平。结论：①肾移植后肾功能恢复正常者其免疫功能仍有异常。②白细胞介素2在亚临床排斥反应发生和抗排干预治疗时变化不明显。③白细胞介素6,8在肾移植亚临床排斥反应的发生、发展中与组织细胞的炎症损伤有关。④白细胞介素10在亚临床排斥反应发生和抗排干预治疗中反应敏感。

BACKGROUND：The occurrence of acute rejection with a typical clinical manifestation is decreased following renal transplantation.However,sub-clinical rejection phenomenon,which characteristics as without significant clinical symptoms and the serum creatinine did not obviously increase or even,is normal,happened frequently,due to the long-term taking course of immunosuppressive agents.OBJECTIVE：To observe the changes of interleukin（IL）-2,IL-6,IL-8,IL-10 and C-reactive protein（CRP）,and their mutual relations in patients with the sub-clinical rejection following renal transplantation.DESIGN,TIME AND SETTING：An observation and controlled trial was performed at Department of Clinical Laboratory,the Second Xiangya Hospital,Central South University from June 2006 to October 2007.PARTICIPANTS：Sixty-eight patients with primary glomerulonephritis who received renal transplantation,including 51males and 17 females,aged 21-60 years were selected.And the time of follow-up was at least 1 year.The other 20 normal cases were served as control.METHODS：According to the clinical symptom,the laboratory immune biochemical indicators,color Doppler ultrasound examination and kidney transplant biopsy,68 cases were divided into sub-clinical rejection group and non-rejection group.Changes of serum cytokines and immune indicators in the non-rejection group and sub-clinical rejection group were observed prior to and after the intervention therapy.MAIN OUTCOME MEASURES：Levels of IL-2,IL-6,IL-8,and IL-10 were detected by enzyme-linked immunosorbent assay（ELISA）,and CRP was analyzed with immunohistochemical rate turbidimetry and IMMAGE automatic immunity analyzer.RESULTS：The levels of serum IL-2,IL-6,IL-8 and IL-10 were higher in patients after renal transplantation than that of the normal control group.When sub-clinical rejection happened,the levels of IL-6,IL-8,and IL-10 were apparently higher than that of non-rejection group（P〈0.01）.After the intervention therapy,IL-2,IL-6 and IL-8 were gradually decreased,and regularly down to the basis levels.The levels of IL-6,IL-8 were significantly correlated to CRP levels（r=0.92,P〈0.01;r=0.85,P〈0.01）.However,IL-10 levels were sharply elevated when the rejection occurred,then decreased,even were lower than the basis levels at one-off time,and gradually rose to the basis levels after intervention therapy.CONCLUSION：①There are still abnormal immune function in patients whose renal function had returned to normal.② IL-2 did not change significantly when sub-clinical rejection occurred and anti-rejection treatment was given.③ IL-6 and IL-8 are correlated to tissue inflammation injury in the occurrence and development of sub-clinical renal transplant rejection.④ IL-10 is sensitive to sub-clinical rejection and anti-rejection treatment.