大鼠肝移植术后早期急性排斥反应与细胞因子基因表达的关系

目的 寻找肝移植术后急性排斥反应的可靠诊断方法。方法 采用袖套技术建立大鼠原位肝移植模型,分为同种异体移植组和同基因移植组,依据病理学变化,对同种异体肝移植术后急性排斥反应作出诊断,应用逆转录多聚酶链反应技术连续检测术后１、２、３、５、７天移植肝内Ｔ淋巴相关性细胞因子ＩＬ－２、ＩＦＮ－γ、ＩＬ－４及ＩＬ－６基因表达。结果 ＩＬ－２及ＩＦＮ－γ的基因表达对急性排斥有特异性,并先于病理学变化。移植肝内     

肾移植后血清白细胞介素2、可溶性白细胞介素2受体和白细胞介素6的监测

动态监测６０例肾移植患者术后２个月内血清白细胞介素２（ＩＬ－２）、可溶性ＩＬ－２受体（ｓＩＬ－２Ｒ）和白细胞介素６（ＩＬ－６）的变化。结果发现发生急性排斥反应时，上述细胞因子的升高较临床诊断提早数天，并且显著高于环孢素Ａ肾中毒组；对甲泼尼龙敏感的排斥反应，抗排斥治疗数天后上述因子下降到排斥前水平。提示肾移植术后动态监测患者血清ＩＬ－２、ｓＩＬ－２Ｒ和ＩＬ－６有助于急性排斥反应的早期诊断、鉴别诊断、及时治疗和甲泼尼龙抗排斥的疗效评价。     

肝癌患者免疫功能的临床研究

通过对１４例肝癌患者围术期ＮＫ细胞、Ｔ细胞亚群，单个核细胞ＩＬ－２Ｒ表达与体液免疫指标ＩｇＧ、ＩｇＡ、ＩｇＭ进行动态测定，结果发现肝癌患者ＮＫ细胞、ＣＤ３细胞、ＣＤ４细胞降低，ＣＤ４／ＣＤ８细胞比值降低，ＣＤ８细胞增高，ＩＬ－２Ｒ表达降低，Ｉｇ升高，后１０天ＮＫ细胞、ＣＤ４细胞、ＣＤ４／ＣＤ８细胞比值、ＩＬ－２Ｒ表达回升。术后３０天升至正常水平；Ｉｇ术后２０天降低，术后３０天至术前水平。结果表明手     

动态监测血清、尿液和肾组织液中SIL－2R水平在肾移植早期的应用价值

为了了解可溶性白介素２受体（ＳＩＬ－２Ｒ）在肾移植早期的应用价值，动态监测４０例肾移植患者血清、尿液及肾组织液中可溶性白介素２受体水平变化，发现术前透析患者血清ＳＩＬ－２Ｒ水平较正常人高，术后迅速下降。急性排斥（ＡＲ）发生时，ＳＩＬ－２Ｒ水平均有不同程度的升高，以肾组织液中升高最明显，比临床症状和血清肌酐出现早１～５天。在急性ＣｓＡ中毒发生时血清和肾组织液中ＳＩＬ－２Ｒ水平明显升高，而急性感染发生时只在血清中明显升高。结果表明：动态监测血清、尿液ＳＩＬ－２Ｒ水平有助于预测和早期诊断ＡＲ，同时行肾组织液及血清、尿液ＳＩＬ－２Ｒ水平测定能较好地诊断与鉴别诊断ＡＲ、急性ＣｓＡ中毒和感染     

监测肾移植术后IL—2和sIL—2R的变化及其意义

对７２例肾移植患者术后血清ＩＬ－２和ｓＩＬ－２Ｒ进行检测，分析移植术后ＩＬ－２和ｓＩＬ－２Ｒ的变化规律，发现在急性排斥和继发感染时，患者血中ＩＬ－２和ｓＩＬ－２Ｒ含量均明显升高。认为监测肾移植术后ＩＬ－２和ｓＩＬ－２Ｒ的变化有助于了解免疫抑制水平和体内免疫系统的功能状态，并可早期诊断急性排斥和继发感染。     

监测肾移植术后IL－2和sIL－2R的变化及其意义

对７２例肾移植患者术后血清ＩＬ－２和ｓＩＬ－２Ｒ进行检测，分析移植术后ＩＬ－２和ｓＩＬ－２Ｒ的变化规律，发现在急性排斥和继发感染时，患者血中ＩＬ－２和ｓＩＬ－２Ｒ含量均明显升高．认为监测肾移植术后ＩＬ－２和ｓＩＬ－２Ｒ的变化有助于了解免疫抑制水平和体内免疫系统的功能状态，并可早期诊断急性排斥和继发感染．     

体外循环手术前后病人血清sIL—2R水平和T淋巴细胞亚群,NK细胞的…

通过检测心脏体外循环手术前后病人血清中可溶性白介素２－受体、Ｔ细胞亚群、自然杀伤细胞，观察分析心脏ＣＰＢ手术病人细胞免疫的影响及其临床意义。选择：２４例风心病择期换瓣病人，术前，ＣＰＢ１０分钟、ＣＰＢ２小时，术后和１天、３天、５天检测血清ｓＩＬ－２Ｒ水平，Ｔ细胞亚群及ＮＫ细胞活性，术后第１天血清ｓＩＬ－２Ｒ水平升高，ＣＯ４（辅助细胞）活性明显降低，ＣＤ４／ＣＤ８（辅助细胞／抑制细胞）比值下降，ＮＫ     

体外循环手术前后病人血清sIL-2R水平和T淋巴细胞亚群、NK细胞的变化及临床意义

目的：通过检测心脏体外循环（ＣＰＢ）手术前后病人血清中可溶性白介素２－受体（ｓＩＬ－２Ｒ）、Ｔ细胞亚群、自然杀伤细胞（ＮＫ），观察分析心脏ＣＰＢ手术病人细胞免疫的影响及其临床意义。方法：选择２４例风心病择期换瓣病人，术前、ＣＰＢ１０分钟、ＣＰＢ２小时、术后第１天、３天、５天检测血清ｓＩＬ－２Ｒ水平、Ｔ细胞亚群及ＮＫ细胞活性。术后第１天血清ｓＩＬ－２Ｒ水平升高，ＣＯ４（辅助细胞）活性明显降低，ＣＤ４／ＣＤ８（辅助细胞／抑制细胞）比值下降，ＮＫ活性降低；并且ｓＩＬ－２Ｒ与ＣＤ４、ＮＫ活性呈负相关。结论：低温心脏ＣＰＢ手术对病人免疫机能有不良影响，临床应采取相应措施，改善术后病人的免疫机能。     

可溶性白介素2受体在肾移植中的作用

用双抗体夹心ＥＬＩＳＡ法对７２例肾移植患者血清可溶性白介素２（ＳＩＬ－２Ｒ）值进行连续动态监测，结果术前尿毒症患者ＳＩＬ－２Ｒ值较正常人高，术后迅速下降，排斥反应时ＳＩＵＬ－２Ｒ值明显升高，与血清肌酐（Ｃｒ）有明显一致性，并较临床症状的出现和血Ｃｒ升高早１－３天，敏感性达９４．４％，特异性达９１．７％，并能与ＣｓＡ中毒相鉴别。术前ＳＩＬ－２Ｒ水平对术后发生排斥反应有一定预示作用，连续动态监测对确定     

HCV感染对肾移植患者T细胞亚群及HLA-DR表达的影响

目的　了解ＨＣＶ 感染对肾移植患者免疫功能及感染和急性排斥反应的影响。　方法　采用直接免疫荧光标记法测定患者外周血Ｔ 细胞亚群及ＨＬＡＤＲ 的表达,并统计ＨＣＶ 感染组和对照组感染和急性排斥反应的发生率。　结果　ＨＣＶ 感染组ＣＤ４ 、ＣＤ２８ 、ＣＤ４／ＣＤ８ 值明显低于无感染组（ 分别为４１ ．３±５ ．１、５５．２ ±５ ．８ 、１．４９±０．４ 和４９ ．１ ±８ ．２ 、６４．８±５．０、１．８１ ±０．５）,ＨＣＶ 感染组Ｔ 细胞ＨＬＡＤＲ 的表达比对照组明显下降（６ ．９ ±４．２ ｖｓ １１．９ ±４．８）,感染和急性排斥反应的发生率两组差异无显著性（分别为２５．０％ 、１０ ．０％ 和１７ ．５％ 、１２．５ ％ ）。　结论　ＨＣＶ 感染可抑制肾移植患者的细胞免疫功能,但不影响患者感染及急性排斥反应的发生率。     

血清sIL-2R、IL-6及胆汁IL-6监测对早期预测肝移植急性排斥反应的作用

目的　评价血清sIL 2R、IL 6及胆汁IL 6水平在预测肝移植急性排斥反应中的意义。方法　连续 3周监测 2 8例肝移植受者术后血清sIL 2R、IL 6及胆汁IL 6水平 ,观察其与急性排斥反应的关系。结果　在急性排斥反应 (AR)组 ,血清sIL 2R及胆汁IL 6水平在排斥发作时明显升高 ,与非排斥组比较有显著性差异 (P <0 .0 1)。当AR经激素冲击治疗逆转后 ,血清sIL 2R及胆汁IL 6下降至排斥前的水平。在AR组 ,仅有 3例受者在排斥发作时血清IL 6水平升高 ,与非排斥组相比 ,血清IL 6水平无明显差异 (P >0 .0 5 )。结论　胆汁IL 6水平有望作为预测AR敏感、较具特异性及非侵袭性的手段。同时 ,其水平还可作为观察抗排异治疗是否有效的指标。     

Determination of the presence of interleukin-6 in bile after orthotopic liver transplantation. Its role in the diagnosis of acute rejection.

OBJECTIVE: The authors evaluated the significance of interleukin-6 (IL-6) in bile in the diagnosis of acute rejection after liver transplantation. SUMMARY BACKGROUND DATA: Interleukin-6 in blood has not been shown to be useful as a marker of acute rejection in clinical liver transplantation. In a rat liver transplantation model, the authors have found that bile IL-6 levels correlated well with the severity of rejection as determined histologically, whereas kinetics of serum IL-6 differed among rats without any definite feature related to graft rejection. METHODS: Fifty-one patients who underwent orthotopic liver transplantation between May 1990 and February 1991 at the University of California, Los Angeles, were included in the study. After liver transplantation, bile and blood were collected daily, and IL-6 levels were measured by the enzyme-linked immunosorbent assay. RESULTS: Bile IL-6 increased to 1228 +/- 317 pg/mL on the day of transplantation and decreased to 50 pg/mL or less within 48 hours. Patients who had uneventful postoperative courses had low levels of bile IL-6 throughout their hospitalization. In patients with acute rejection, bile IL-6 significantly increased (1090 +/- 990 pg/mL; p<0.05), but decreased in response to antirejection therapy. In patients who had liver dysfunction due to ischemic change or sepsis, bile IL-6 did not increase. Patients with cholangitis had significantly increased levels of bile IL-6 (146 +/- 47; p<0.05). Interleukin-6 in blood increased with many kinds of complications other than rejection and seemed to be less specific than that in bile. CONCLUSIONS: Measurement of IL-6 in bile may be a useful, noninvasive tool for diagnosing acute rejection.     

Cytokine gene polymorphisms and acute liver graft rejection: a meta-analysis.

In the field of liver transplantation, 7 reports have been published investigating the association between polymorphisms in cytokine genes and the occurrence of acute rejection in liver graft recipients. However, most of the individual studies lack the statistical power to detect a small-to-moderate effect of cytokine gene polymorphisms on the acute rejection rate. To overcome this problem, we performed a quantitative meta-analysis of 7 gene-association studies that were comparable with regard to definition of acute rejection and the type of immunosuppression used. In the overall analysis, the interleukin (IL)-10 polymorphism at position -1082 was identified as a genetic risk factor for acute liver graft rejection; liver transplant recipients carrying the IL-10 -1082.A allele displayed a lower rejection rate (common odds ratio [OR], .6; 95% confidence interval [CI], .4-.9). For the tumor necrosis factor (TNF)-A -308 polymorphism, a common OR could not be calculated due to significant heterogeneity of ORs between the studies (mean OR, 1.4; 95% CI, .8-2.6). No associations were found between acute liver graft rejection and single nucleotide polymorphisms in the IL-6 (position -174) and transforming growth factor (TGF)-beta1 (positions +869 and +915) genes. In conclusion, results from this meta-analysis suggest a role for the IL-10 -1082 polymorphism in human liver graft rejection.     

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目的前瞻性地观察肝移植术后早期应用重组生长激素(rhGH)的有效性和安全性。方法将2003年1～10月在中山大学器官移植研究所肝移植中心接受原位肝移植的30例良性终末期肝移植病人随机分为观察组和对照组两组,观察组于术后第1天开始连续7d每天1次皮下注射重组人生长激素10U,其它治疗与对照组相同。术前及术后1、4、8、14天测定生化、免疫和营养等指标,并观察两组的感染率和排斥率。结果观察组术后第4、8、14天血清测定生长激素(GH)、胰岛素样生长因子-1(IGF1)水平较对照组显著升高(P<0.05);而术后4、8天谷丙转氨酶(ALT)、血清尿素氮(BUN)和转铁蛋白较对照组显著降低(P<0.05)。观察组感染率较对照组降低,但两组差异无显著性,同时两组血清IgG,IgM,IgA,IL2水平CD4/CD8值及急性排斥反应发生率差异均无显著性(P>0.05)。结论rhGH能促进肝移植术后肝细胞损伤的修复与GH-IGF-1轴的恢复,能适当降低术后感染率且未增加急性排斥反应发生率。     

Acute lung transplant rejection is associated with localized increase in T-cell IFNgamma and TNFalpha proinflammatory cytokines in the airways

BACKGROUND: Allograft rejection remains a major cause of morbidity and mortality after lung transplantation and is associated with increased gene expression for proinflammatory cytokines. T cells are a major cell type involved in graft rejection. There have been no previous studies of cytokine production by T cells from blood, bronchoalveolar lavage (BAL), and intraepithelial T cells from bronchial brushings (BB) during rejection episodes; we hypothesized that T-cell proinflammatory cytokines would be increased in the airways during rejection episodes despite standard immunosuppression regimens. METHOD: To investigate changes in cytokine profiles during rejection episodes, whole blood, BAL, and BB from stable lung transplant patients and those with acute rejection were stimulated in vitro and intracellular cytokine production by CD8- (CD4+) and CD8+ T-cell subsets determined using multiparameter flow cytometry. RESULTS: Transforming growth factor (TGF)-beta was significantly decreased in blood CD4+ and CD8+ T cells while interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were significantly increased in BAL CD4+ and CD8+ T cells in patients with evidence of rejection. There was no change in CD4:CD8, interleukin (IL)-2, or IL-4 between stable and rejecting groups. CONCLUSIONS: Acute lung transplant rejection is associated with decreased intracellular T-cell TGFbeta in blood and increased intracellular IFNgamma and TNFalpha in BAL CD4+ and CD8+ T cells. Drugs that effectively reduce airway T-cell IFNgamma and TNFalpha proinflammatory cytokine production may improve current protocols for reducing acute graft rejection in lung transplant patients.     

胆汁可溶型抑制性受体LAIR-1以及白介素-2受体监测在肝移植急性排斥反应中的意义

目的 探讨胆汁中sLAIR-1及IL-2R的表达在肝移植排斥反应中的意义.方法 连续3周应用双单克隆抗体夹心ELISA方法检测55例肝移植受者术后胆汁sLAIR-1及sIL2R水平.结果 在22例移植肝功能正常的受体中(对照组),胆汁sIL-2R在(23.1±3.5)～(55.1±6.1)ng/L范围之内呈较低水平的波动,sLAIR-1则波动于(3.2±1.1)～(6.1±1.4)ng/L范围之内,亦呈低水平表达.在急性排斥反应(AR)组,胆汁sIL-2R水平在排斥反应确诊前2 d为(116.1±10.3)ng/L,确诊前1 d则为(136.8±12.7)ng/L,均显著高于对照组(P＜0.01).在经激素冲击治疗3 d时则下降至(74.2±6.2)ng/L,明显低于确诊前1、2 d水平.在对照组,胆汁sLAIR-1在(3.2±1.1)～(6.1±1.4)ng/L范围之内呈较低水平的波动;在AR组确诊前3 d为(18.1±2.2)ng/L,确诊前2 d为(25.1±3.5)ng/L,确诊前1 d则为(31.1±5.5)ng/L,均显著高于对照组(P＜0.01);经激素冲击治疗3 d时,胆汁sLAIR-1水平下降至(8.1±2.5)ng/L,接近对照组水平,且sLAIR-1的下降早于sIL2R.结论 胆汁sLAIR-1在发生移植肝急性排斥反应的病人血清中有较高水平的表达,其波动较sIL-2R大,将二者联合进行监测,可望成为早期预测移植物排斥反应发生及转归的诊断指标.     

胆汁可溶型抑制性受体LAIR-1以及白介素-2受体监测在肝移植急性排斥反应中的意义

目的 探讨胆汁中sLAIR-1及IL-2R的表达在肝移植排斥反应中的意义.方法 连续3周应用双单克隆抗体夹心ELISA方法检测55例肝移植受者术后胆汁sLAIR-1及sIL2R水平.结果 在22例移植肝功能正常的受体中(对照组),胆汁sIL-2R在(23.1±3.5)～(55.1±6.1)ng/L范围之内呈较低水平的波动,sLAIR-1则波动于(3.2±1.1)～(6.1±1.4)ng/L范围之内,亦呈低水平表达.在急性排斥反应(AR)组,胆汁sIL-2R水平在排斥反应确诊前2 d为(116.1±10.3)ng/L,确诊前1 d则为(136.8±12.7)ng/L,均显著高于对照组(P＜0.01).在经激素冲击治疗3 d时则下降至(74.2±6.2)ng/L,明显低于确诊前1、2 d水平.在对照组,胆汁sLAIR-1在(3.2±1.1)～(6.1±1.4)ng/L范围之内呈较低水平的波动;在AR组确诊前3 d为(18.1±2.2)ng/L,确诊前2 d为(25.1±3.5)ng/L,确诊前1 d则为(31.1±5.5)ng/L,均显著高于对照组(P＜0.01);经激素冲击治疗3 d时,胆汁sLAIR-1水平下降至(8.1±2.5)ng/L,接近对照组水平,且sLAIR-1的下降早于sIL2R.结论 胆汁sLAIR-1在发生移植肝急性排斥反应的病人血清中有较高水平的表达,其波动较sIL-2R大,将二者联合进行监测,可望成为早期预测移植物排斥反应发生及转归的诊断指标.     

胆汁可溶型抑制性受体LAIR-1以及白介素-2受体监测在肝移植急性排斥反应中的意义

目的 探讨胆汁中sLAIR-1及IL-2R的表达在肝移植排斥反应中的意义.方法 连续3周应用双单克隆抗体夹心ELISA方法检测55例肝移植受者术后胆汁sLAIR-1及sIL2R水平.结果 在22例移植肝功能正常的受体中(对照组),胆汁sIL-2R在(23.1±3.5)～(55.1±6.1)ng/L范围之内呈较低水平的波动,sLAIR-1则波动于(3.2±1.1)～(6.1±1.4)ng/L范围之内,亦呈低水平表达.在急性排斥反应(AR)组,胆汁sIL-2R水平在排斥反应确诊前2 d为(116.1±10.3)ng/L,确诊前1 d则为(136.8±12.7)ng/L,均显著高于对照组(P＜0.01).在经激素冲击治疗3 d时则下降至(74.2±6.2)ng/L,明显低于确诊前1、2 d水平.在对照组,胆汁sLAIR-1在(3.2±1.1)～(6.1±1.4)ng/L范围之内呈较低水平的波动;在AR组确诊前3 d为(18.1±2.2)ng/L,确诊前2 d为(25.1±3.5)ng/L,确诊前1 d则为(31.1±5.5)ng/L,均显著高于对照组(P＜0.01);经激素冲击治疗3 d时,胆汁sLAIR-1水平下降至(8.1±2.5)ng/L,接近对照组水平,且sLAIR-1的下降早于sIL2R.结论 胆汁sLAIR-1在发生移植肝急性排斥反应的病人血清中有较高水平的表达,其波动较sIL-2R大,将二者联合进行监测,可望成为早期预测移植物排斥反应发生及转归的诊断指标.     

Acute rejection after liver transplantation: Is there a specific immunological pattern?

The aim of the study was to assess various T-cell subsets and cytokine secretion patterns both in liver tissue and in the peripheral blood of 24 liver transplant patients to assess possible specific immunological involvement in early acute rejection episodes after liver transplantation. Particularly, we studied CD4+ CD7+, CD8+ CD38+, and CD4+ CD25+ T cells by flow cytometry, as well as contemporaneously, interleukin (IL)-2 and IL-10 secretion by ELISpot to determine possible Th1-like immune responses and the immunomodulation expressed by Treg cells in acute liver rejection, respectively. As a control group we included patients transplanted without acute rejection. Early acute rejection within the first 4 weeks was proven histologically in 42% of patients. It was associated with a greater expression of CD4+ CD7+ and CD8+ CD38+ T cells in the liver than in the blood (P < .001). A contemporaneous reduced expansion of liver Treg cells was evident in patients with acute rejection (P < .001). Our data suggested that a preferential Th1-like immune mechanism operated in local fashion as characterized by a decreased presence in the liver and blood of Treg cells.