可溶性CD30联合血清肝细胞生长因子检测诊断移植肾急性排斥

目的 探讨肾移植术前可溶性CD30(sCD30)联合术后第5天血清肝细胞生长因子(HGF)检测诊断肾移植术后急性排斥反应(AR).方法 采用酶联免疫吸附法对65例肾移植患者术前sCD30水平及术后第5天的HGF水平进行检测.依据术前sCD30水平将患者分为sCD30阳性受者及sCD30阴性受者.通过分析特征工作曲线(ROC)评价第5天的HGF水平诊断移植肾AR的意义,进一步分析sCD30联合HGF诊断AR的价值.结果 65例患者术后26例发生AR为排斥反应组,39例顺利恢复,为无排斥反应组.以sCD30值120U/ml为界限值,排斥反应组sCD30阳性率为61.5%,无排斥反应组阳性率为17.9%,有显著差异(P＜0.05).排斥反应组和无排斥反应组肾移植术后第5天的HGF水平差别有统计学意义(P＜0.05),ROC证明HGF界限值90μg/L可较好的诊断移植肾急性排斥反应,敏感度84.6%,特异度76.9%.联合术前sCD30的结果.可提高AR的诊断效果.结论 sCD30联合HGF检测分析可有效诊断肾移植AR.     

人类白细胞抗原G及其受体在肾移植术后监测的临床意义

目的 探讨人类白细胞抗原G(HLA-G)作为判断肾移植预后的生物标记物的价值并分析HLA-G受体的表达与HLA-G作用机制的相关性.方法 选取2006年2月至2008年6月解放军第三○九医院全军器官移植中心施行初次肾移植受者215例,根据术后临床状况分为肾功稳定组(n=173)和急性排斥组(n=42),采集外周血用酶联免疫吸附试验(ELISA)法检测可溶性人类白细胞抗原G5(sHLA-G5)表达含量,流式细胞术分析HLA-G受体免疫球蛋白样受体2(ILT-2)在T、B淋巴细胞的表达及杀伤细胞免疫球蛋白样受体(KIR)2DL4在自然杀伤(NK)细胞的表达.采用受试者工作特征(ROC)曲线运算sHLA-G5阈值,预测肾移植术后排斥反应.运用回归分析验证sHLA-G5与急性排斥反应发生的相关性.结果 sHLA-G5水平预测急性排斥反应组的最适域值为139.0μg/L,其敏感度为63.6%,特异度为82.1%,曲线下面积(AUC)为0.780.二元Logistic回归分析显示sHLA-G5是肾移植术后急性排斥反应发生的独立影响因素(P=0.019,OR=0.039,95%可信区间为2.091～5.661).急性排斥组CD4+T细胞、CD8+T细胞、B细胞表面的ILT-2表达均低于肾功稳定组(21%±7%比52%±17%,23%±6%比39%±16%,21%±7%比39%±16%,均P＜0.05).急性排斥组NK细胞表面的KIR2DLA表达也低于肾功稳定组(31%±10%比57%±21%,P＜0.05).结论 sHLA-G5表达水平对预测肾移植术后排斥反应具有较高的敏感度和特异度,HLA-G诱导免疫耐受的机制可能与淋巴细胞表面ILT-2、KIR2DLA的高表达密切相关.     

肾移植受者术前血清可溶性CD30水平与受者及移植物长期存活的关系

目的研究术前血清可溶性CD30(sCD30)水平与肾移植受者及移植物长期存活的关系。方法共纳入自1998年12月至2003年8月行同种异体肾移植手术且存有术前血标本的707例受者。回顾性总结该组受者术后长期存活及其他基线资料,用sCD30酶联免疫吸附试验(ELISA)试剂盒复孔检测肾移植受者术前血清sCD30水平。结果低、中、高sCD30组的5年肾存活率分别为84.7%±2.1%、88.1%±2.9%和77.7%±3.5%,5年功能性存活率为98.9%±1.1%,95.1%±1.6%和85.0%±3.2%。高sCD30组的移植肾的长期存活/功能性存活均明显低于低、中sCD30组(均P<0.05),但中sCD30组的人长期存活率最高,低、中、高sCD30组的5年人存活率分别为84.7%±3.9%,92.4%±1.6%和87.1%±2.7%。死亡原因均主要为感染、肝功能衰竭和心脑血管意外,但3组在死亡前1个月内发生急性排斥反应分别占死亡人数的0、13.0%和40.9%。结论术前sCD30水平与肾移植受者的免疫状态有关,高sCD30代表受者高免疫反应性,预示术后急性排斥反应的发生率增高而导致移植肾预后不良;而低sCD30表示机体相对的免疫功能低下而处于感染和药物毒性的高风险中。     

利用肾移植受者术后血清可溶性CD30预测早期急性排异反应

目的:评价利用肾移植受者术后血清可溶性CD30(sCD30)水平预测急性排异反应的可行性.方法:利用ELISA方法分别在术前、术后5 d和10 d检测231名肾移植受者的血清sCD30水平,根据肾移植受者术后1 mo内临床表现将他们分为三组:急性排异反应组(AR,n=49),肾功能延迟恢复组(DGF,n=11)和正常组(UC,n=171).结果:231名肾移植受者的血清sCD30水平由术前的(178±79)U/mL分别降至术后5 d的(52±30)U/mL和术后10 d的[(9±5)U/mL,P<0.001].AR组术后5 d的sCD30水平为(92±27)U/mL,高于uc组(41±20)U/mL和DGF组[(48±18)U/mL,P<0.001].而术前和术后10 d的sCD30水平在三组患者之间的差异无统计学意义.ROC曲线分析结果表明,利用术后5 d sCD30水平可以预测近期内即将出现的急性排异反应(曲线下面积0.95).并且,根据ROC曲线分析得出:将65 U/mL作为临界点可以较好的预测急性排异反应(特异性91.8%,敏感性87.1%).结论:检测肾移植受者术后5 d的血清sCD30水平可以预测移植后早期出现的排异反应.     

sCD30表达与移植肾慢性排斥反应的关系

目的探讨肾移植受者sCD30(soluble CD30)表达与移植肾慢性排斥反应的关系。方法用ELISA方法对80例肾移植2年以上受者血样进行sCD30定量测定,同时进行移植肾穿刺活检、PRA、血环孢素A浓度、血肌酐检测。结果移植肾慢性排斥反应发生组sCD30表达水平明显高于无慢性排斥组,差异有统计学意义(P<0.05)。高sCD30组中慢性排斥反应发生率明显高于低sCD30组慢性排斥反应发生率,差异有统计学意义(P<0.05),且高sCD30与低sCD30受者相比其PRA阳性率并无统计学意义(P>0.05)。结论检测sCD30对判断移植肾慢性排斥反应发生有指导意义,且可能不受PRA影响。     

sCD30动态监测在移植肾急性排斥反应时的意义

[摘要] 目的 探讨血清可溶性CD30（sCD30）水平在肾移植术后急性排斥反应（AR）的变化及意义。方法 采用酶联免疫吸附法对肾移植术后22例发生AR的患者及20例顺利恢复,无排斥反应的患者sCD30水平进行动态监测，观察比较两组患者sCD30的变化规律。结果 排斥反应组术后具有较高的sCD30水平，和无排斥反应组相比在术后第5d、第7d有统计学意义(P<0.05)。排斥反应组sCD30水平在糖皮质激素冲击治疗后下降，但耐糖皮质激素性排斥者的下降速度较糖皮质激素敏感性排斥者缓慢，冲击治疗后的sCD30差异具有显著性(P<0.05)。结论 sCD30水平变化可作为肾移植AR的诊断指标及判断排斥反应对糖皮质激素冲击治疗是否敏感。     

血清可溶性CD3和群体反应性抗体与肾移植术后早期急性排斥反应的关系

目的探讨血清可溶性CD30(sCD30)和群体反应性抗体(PRA)检测在预测肾移植术后早期急性排斥反应中的意义。方法采用酶联免疫吸附法(ELISA)检测42名肾移植受者术前外周血sCD30和PRA水平。对明确有排斥反应、可疑有排斥反应以及不能区分排斥反应的患者在B超引导下行移植肾活检穿刺病理检查。结果穿刺证实为急性排斥(BPAR)反应组(n=16)sCD30值(185.3±42.6)U/mL显著高于非排斥组n=26,(75.3±22.7)U/mL,(P<0.005)。当sCD30和PRA阳值分别定为大于100U/mL和大于10%时,sCD30和PRA预测发生急性排斥反应的灵敏度56.3%对31.3%、特异度92.3%对92.3%、准确度78.6%对69.0%、阳性预测值81.8%对71.4%、阴性预测值77.4%对68.6%,sCD30阳性组和PRA阳性组发生急性排斥反应的相对危险度为3.6对2.3。结论sCD30和PRA阳性是术后早期发生急性排斥反应的高危因素,sCD30与PRA相比更有助于预测术后早期发生急性排斥反应的危险性。     

肾移植受者血清可溶性HLA-Ⅰ类抗原的动态监测

据《中华外科杂志》1999年11月37卷第11期报道 为了解血清可溶性HLA-Ⅰ类抗原(sHLA-Ⅰ)与肾移植受者发生急性排斥反应及感染的关系,第一军医大学南方医院肾移植科徐健等应用酶联免疫法对36例肾移植受者的sHLA-Ⅰ水平进行了动态监测。结果显示,尿毒症组sHLA-Ⅰ水平为(2.94±0.34)μg/L,     

ROC曲线评价血清IGF-1在胶质瘤中的诊断价值

目的运用ROC曲线评价胰岛素样生长因子(IGF-1)在诊断胶质瘤中的应用价值。方法选取胶质瘤、非胶质来源肿瘤及健康对照组各40例。采用ELISA法对3组患者血清中的IGF-1进行定量检测,比较3组结果间的差异,评估胶质瘤的诊断临界值。结果非胶质来源肿瘤组血清IGF-1水平(37.77±46.29)μg/L和健康对照组(26.98±27.63)μg/L比较差异无统计学意义(P>0.05)。胶质瘤组血清IGF-1水平(643.13±792.19)μg/L显著高于非胶质来源肿瘤组和健康对照组(63.52±101.53)μg/L(P<0.01)。对实验数据进行ROC曲线分析显示,IGF-1诊断胶质瘤的ROC曲线下面积(AUC)为0.831(95%CI0.745～0.917),诊断临界值为110.425μg/L,其诊断敏感度为90.0%,诊断特异度为92.3%,阳性预期值为87.5%,阴性预期值为92.3%,正确率为90.5%,Youden值为82.3%。结论 IGF-1在诊断胶质瘤中具有较高的敏感度和特异度,可作为胶质瘤诊断指标之一。但由于IGF-1的局限性,寻求另一种或多种胶质瘤相关的血清标记物与IGF-1联合检测更具有意义。     

人类白细胞抗原G在肾移植受者外周血的表达探讨

目的 探讨人类白细胞抗原(HLA)G的膜型HLA-G(mHLA-G)、胞内HLA-G(iHLA-G)和可溶型HLA-G(sHLA-G)在肾移植受者外周血的表达及其与术后临床相关性.方法 研究对象为2000年2月至2006年6月解放军第三零九医院全军器官移植中心行肾移植的175例受者,根据4周内是否发生排斥反应分为急性排斥反应组(36例)、功能稳定组(139例),30例健康供者作为对照组.应用流式细胞术检测外周血mHLA-GI、iHLA-G1的表达,酶联免疫吸附法检测血浆sHLA-G5的含量.结果 T淋巴细胞CD~+ mHLA-G1~+、CD8~+ mHLA-G1~+、CD4~+ iHLA-G1~+、CD8~+ iHLA-G1~+平均表达率在对照组分别为0.43%±0.19%、1.23%±0.41%、27%±13%、36%±14%,急性排斥反应组分别为:0.57%±0.34%、1.31%±0.56%、26%±8%、37%±17%,功能稳定组分别为0.61%±0.43%、1.39%±0.47%、26%±9%、37%±17%,3组间比较差异均无统计学意义(均P>0.05).外周血浆sHLA-G5表达在对照组为(25±14)ng/ml;急性排斥组术前为(24±15)ng/ml,术后为(34±21)ng/ml;功能稳定组术前为(25±11)ng/ml,术后为(56±32)ng/ml;急性排斥组和功能稳定组术前与健康组比较,差异无统计学意义(P>0.05),术后功能稳定组明显高于急性排斥组(P<0.05).结论 肾移植受者外周血存在一群比率较低的HLA-G~+ T淋巴细胞,mHLA-G1和iHLA-G1的表达与肾移植术后的排斥反应发生无关,sHLA-G5的高表达与排斥反应发生的减少有关.     

Effect of pre-transplantation hemoglobin concentration on prognosis of renal transplant recipients

Background  For the renal transplant recipients, anemia is one of the common complications and becomes a major medical issue before transplantation. Haemoglobin (Hb) is used as a prognostic indicator, although the optimal pre-transplantation Hb concentration associated with positive prognosis is still controversial. The aim of this study was to detect the optimal Hb concentration on predicting the graft survival and function.

Methods  A retrospective cohort study was conducted by reviewing the medical records of the patients who received renal transplantations at our center from January 2004 to June 2008. Patients were divided into two groups: high Hb group (≥100 g/L, n=79) and low Hb group (<100 g/L, n=63). There was no significant difference between the two groups regarding sex, age, blood type and tissue types. Renal function among the two groups was measured and compared. Panel reacting antigens (PRA) of all the recipients were negative. The effect of preoperative hemoglobin concentration on the postoperative renal function recovery in both groups was further analyzed.

Results  A total of 14 acute rejection episodes occurred, including 5 patients in the high Hb group (7.9%) and 9 in the low Hb group (11.4%, P >0.05). The serum creatinine level at one-year post-transplantation of the low Hb group was significantly higher than that of the high Hb group ((117.8±36.3) μmol/L vs. (103.1±35.5) μmol/L, P <0.05). For one-year actuarial patient and graft survival, incidence of delayed graft function (DGF), serum creatinine concentrations at 1, 3, 6 months post-transplantation, the incidence of cytomegalovirus (CMV) infection, post-transplantation anemia (PTA) and post-transplantation diabetes mellitus (PTDM) of both groups, there were no statistically significant differences.

Conclusion  Pre-transplantation Hb concentration has significant effect on one-year creatinine concentration, but can not significantly affect acute rejection episodes, DGF, PTA, CMV infection and PTDM.

     

人鼠嵌合型抗IL-2R单克隆抗体诱导肾移植受者sHLA-G5的表达上调

目的 探讨可溶性人类白细胞抗原G5(sHLA-G5)的表达上调是否为肾移植受者应用抗白细胞介素2受体(IL-2R)单克隆抗体的一个新的作用机制.方法 选取2006年1月至2007年12月解放军第三○九医院全军器官移植中心施行初次肾移植受者215例,根据是否使用抗IL-2R单克隆抗体分为:抗体使用组141例,抗体未使用组74例.健康对照组69例.采集外周血用酶联免疫吸附试验(ELISA)法检测sHLA-G5表达含量,并应用蛋白印迹方法和实时定量聚合酶链反应(Realtime PCR)进行验证.结果 移植术前,抗体使用组抗体使用后sHLA-G5的表达[(56±30)μg/L]高于抗体使用前[(34±20)μg/L],也高于健康对照组[(35±17)μg/L]和抗体未使用组[(36±19)μg/L,均P＜0.05].移植术后1 d、4 d、1周、2周,抗体使用组sHLA-G5表达随时间呈现上升趋势;而抗体未使用组sHLA-G5的表达术前术后波动很小,但术后各时间点抗体使用组sHLA-G5的表达均明显高于抗体未使用组[(95±35)μg/L比(54±16)μg/L;(131±24)μg/L比(75±22)μg/L;(167±44)μg/L比(62±17)μg/L;(172±35)μg/L比(45±16)μg/L,均P＜0.01].蛋白印迹法和PCR结果与ELISA法结果相一致.结论 肾移植受者早期应用抗IL-2R单克隆抗体能够诱导sHLA-G5的表达上调,这种调节利于移植物存活,降低排斥反应发生的可能性.

Abstract：

Objective To find whether the up-regulation of soluble human lecocyte antigen-G5 (sHLA-G5) levels is a new function mechanism of anti-interleukin-2 receptors (anti-IL-2R) monoclonal antibody treatment in kidney transplantation. Methods A total of 215 recipients at our centre from January 2006 to December 2007 were divided into antibody use group ( n = 141 ) and antibody non-use group ( n =74) and another healthy group (n =69). The sHLA-G5 level in peripheral blood was detected by enzymelinked immunosorbent assay (ELISA). And the expression of HLA-G5 was confirmed by Western blot and Real-time polymerase chain reaction (PCR). Results sHLA-G5 levels was (56 ± 30)μg/L in using antiIL-2 receptor monoclonal antibody before transplantation, It was higher than that before use antibody [(34 ±20) μg/L], also higher than healthy group [(35 ± 17) μg/L] and antibody non-use group [(36 ± 19)μg/L, P ＜0. 05, respectively]. At Day 1, Day 4, Week 1, Week 2 post-transplantation, the level of sHLA-G5 of recipients with antibody use was significantly higher than that of those with antibody non-use. The values were as follows: (95 ±35) μg/L vs (54 ± 16) μg/L , (131 ±24) μg/L vs (75 ±22) μg/L ,(167±44) μg/L vs (62 ± 17) μg/L, (172 ±35) μg/L vs (45 ±16) μg/L(all P＜0.01). And the results of Western blot and RT-PCR corresponded to those of ELISA. Conclusion The preoperative use of first dose of anti-IL-2R monoclonal antibodies results in the up-regulated level of sHLA-G5. Thus it is beneficial for protecting the kidney survival and reducing the risks of acute rejection.     

微嵌合体在母亲子女之间活体肾移植中的作用

目的 观察不同供受体关系亲属活体肾移植的临床疗效及其与微嵌合体之间的关系.方法 回顾性分析复旦大学附属中山医院2004-2008年130例亲属肾移植临床资料.受者随访1～5年,利用微卫星及性染色体决定基因聚合酶链反应(PCR)技术检测外周血DNA微嵌合体,并根据随访结果,分析微嵌合体的作用.结果 受者1-年人/肾存活率分别为93.8%和92.3%,各供受者组关系比较发现1-年人/肾存活率差异均无统计学意义(均P＞0.05).130例受者中46例(35.4%)行移植肾穿刺活检,病理结果证实发生急性排斥反应26例,急性排斥反应发生率为20.0%(26/130).26例中14例(53.8%)为母亲子女之间肾移植,12例(46.2%)为其他供受者关系肾移植.母亲子女肾移植中急排斥反应发生率为30.4%(14/46),高于其他供受者关系肾移植急性排斥反应发生率(14.3%,12/84,P=0.028).130例受者中43例术后不同时间进行了外周血微嵌合体检测,在其中16例母亲供肾的受者中,4例检测到微嵌合体,阳性率25.0%;27例其他供者的受者中,4例检测到微嵌合体,阳性率为14.8%;母亲供肾微嵌合体阳性率比其他关系高约1倍.微嵌合体阳性组急性排斥反应发生率较微嵌合体阴性组高约1倍.结论 母亲子女之间肾移植急性排斥发生率较高;母亲供肾的微嵌合率较高;微嵌合率高的组别急性排斥反应较高;母亲子女之间特殊的免疫学关系可能影响肾移植效果.

Abstract：

Objective To compare the microchimeric and rejection rates in living donor kidney transplant recipients in mother and child relations and other relations. Methods This retrospective singlecenter study enrolled 130 recipients to receive allografts from living related donors from 2004 to 2008 at our hospital. They were followed up for 1 - 5 years. The demographic data of the study population were analyzed by basic statistical methods. A total of 43 recipient blood samples were collected for the detection of microchimerism by the assays of short tandem repeat (STR) and sex-determining region-y gene (SRY)polymerase chain reaction (PCR). Results The 1-year patient/graft survival rates were 93.8% and 92.3% respectively. And there was no significant differences between mother and child group and other relative group. Forty-six biopsy samples were collected from 46 recipients. Twenty-six (20.0% ) cases had the occurrences of acute rejection episodes in different Banff degrees as proven by biopsy. 53. 8% ( 14/26)cases were mother and child renal transplantation, higher than other relative (46. 2%, 12/26) . The mother donor kidney transplant recipients had about a twice higher rejection rate ( 30.4% vs 14. 3%, P = 0.028 ) and a twice higher microchimeric rate(25. 0% vs 14. 8% )than other relative. Conclusion Compared with other relations, the mother donor kidney recipients tend to have higher rates of microchimerism and acute rejection. And the special immune effect in mothers and children renal transplantation may influence its outcomes.     

HLA-G expression in the peripheral blood of live kidney transplant recipients

Background The human leukocyte antigen-G (HLA-G) has been considered to be an important tolerogeneic molecule playing an essential role in maternal-fetal tolerance, upregulated in the context of transplantation, malignancy, and inflammation, and has been correlated with various clinical outcomes. The aim of this study was to investigate the clinical relevance of the expression of membrane HLA-G (mHLA-G), intracellular HLA-G (iHLA-G), and soluble HLA-G (sHLA-G) in the peripheral blood of live kidney transplant recipients.

Methods We compared the expression of the three HLA-G isoforms in three groups, healthy donors (n=20), recipients with acute rejection (n=19), and functioning transplants (n=30). Flow cytometry was used to detect the expression of mHLA-G and iHLA-G in the T lymphocytes of peripheral blood from subjects in the three groups. Enzyme-linked immunosorbent assays were used to detect sHLA-G in the plasma from the three groups.

Results There were no significant differences in mHLA-G and intracellular HLA-G among the three groups, but the sHLA-G plasma level was higher in the functioning group than in the acute rejection or healthy group. We found a subset of CD4+HLA-G+ and CD8+HLA-G+ T lymphocytes with low rates of mHLA-G expression in the peripheral blood of kidney transplantation recipients. Intracellular expression of HLA-G was detected in T lymphocytes. However, there was no correlation between acute rejection and the mHLA-G or intracellular HLA-G expression.

Conclusion sHLA-G was the major isoform in the peripheral blood of live kidney transplant recipients and high sHLA-G levels were associated with allograft acceptance.

     

舒莱预防肾脏移植物急性排斥反应的随机对照试验研究

目的：探讨白细胞介素2受体单克隆抗体——舒莱（Simulect）对移植肾急性排斥反应的预防作用以及用药的安全性与药物的毒副作用。方法：将我器官移植移植中心1999年3月～2002年10月共46例肾移植受者为研究对象，随机分成舒莱组（23例）和对照组（23例），两组肾移植术后均接受以Neoral为基础的三联免疫抑制剂。舒莱组术前2h和术后4d各给予舒莱20mg静脉滴注。观察急性排斥反应、Neoral、皮质激素和硫唑嘌呤用量及药物的毒副作用。实验室检测血CsA浓度和肝肾功能。结果：研究结果表明，舒莱组无1例发生急性排斥反应，对照组术后8周内发生3例4次急性排斥反应。两组均未发生明显的毒副作用。两组间Neoral用量及血CsA浓度无明显差异。对照组因发生急性排斥反应，8周内皮质激素用药量总量大于舒莱组。结论：舒莱对移植肾急性排斥反应具有明显的预防作用，且用药方法简便，疗程短，无明显的毒副作用。     

肾移植术后贫血的危险因素分析

【目的】 探讨肾移植术后贫血(PTA)的发生率&#65380;风险因素&#65377; 【方法】 分析2004年1月至2008年6月在本院进行肾移植术的患者资料,并根据术后是否发生PTA将患者分成PTA组(44例)及对照组(132例),记录可能引起PTA的各项参数,分别用t检验和?字2检验进行单因素分析,对P < 0.2的参数进行Logistic多因素分析,计算其相对危险度(RR)及95%可信区间(95%CI)&#65377;【结果】 PTA(男性血红蛋白(Hb) < 120 g/L或红细胞压积(Hct) < 0.38或成年女性Hb < 110 g/L或Hct < 0.35)在本中心的发病率为31%&#65377;单因素及Logistic多因素回归分析表明:女性(RR = 8.738;95%CI 2.558 ~ 29.853; P = 0.001);平均肌酐水平(RR = 1.035;95%CI 1.018 ~ 1.052;P < 0.001)以及急性排斥(RR = 19.827;95%CI 2.056 ~ 191.19;P = 0.01)等3项因素与PTA的发生密切相关&#65377;【结论】 PTA是肾移植术后一项常见的并发症,女性&#65380;移植肾功能较差以及急性排斥的发生是PTA的危险因素&#65377;