交叉反应组(CREGs)配型原则在肾移植中的应用研究

目的：探讨交叉反应组（CREGs）配型在肾移植中的应用价值。方法：对173例肾移植患者分别采用CREGs配型原则和HLA配型原则的配型情况并对其术后急性排斥反应情况进行相关分析。结果：HLA配型A、B、DR位点0（抗原错配）MM的比率分别为7.51%、4.04%、3.46%,2MM的比率分别为39.88%、65.31%、58.38%;而应用CREGs配型A、B、DR位点0MM的比率分别为49.71%、30.63%、24.27%,2MM的比率分别为5.20%、12.14%、8.67%。HLA配型A、B、DR位点0MM急性排斥反应发生率分别为21.96%、21.38%、7.51%,2MM分别为22.54%、20.23%、66.67%;CREGs配型A、B、DR位点0MM急性排斥反应发生率分别为21.83%、20.21%、6.14%,2MM分别为22.22%、20.00%、69.82%。结论：CREGs配型原则能够有效提高供肾利用率,是一种新的选择肾移植供-受者的配型的方法。     

HLA配型、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：研究人类白细胞抗原(HLA)配型、群体反应性抗体(PRA)与肾移植术后早期急性排斥反应的关系。方法：应用单克隆抗体板、微量序列特异性引物、混合抗原板进行供受者HLA-I类抗原分型、HLA-Ⅱ类基因分型、PRA检测。结果：PRA为低、中、高三组受者的早期急性排斥反应发生率分别为16％、27％、66．6％。HLA位点错配数(MM)为0-1组明显比5—6组早期急性排斥反应率低。结论：良好的组织配型、低水平的PRA，可降低早期急性排斥反应的发生。     

肾移植受者HLA体液免疫致敏状态的监测及其临床意义

为探讨肾移植受者同种异体HLA抗原致敏后体液免疫状态与术后排斥反应及移植物存活率的相关性及其临床意义,应用One Lambda混合抗原板(LATM)通过ELISA筛查受者术前血清中的HLA-IgG抗体,对阳性血清进一步用抗原板(LAT1240和LAT1HDS)检测抗体阳性率及其特异性;并采用序列特异性引物聚合酶链反应(PCR-SSP)技术进行HLA基因分型。在1 297例肾移植受者中,HLA-IgG抗体阳性者165例,其中I类抗体阳性126例,II类抗体阳性90例,51例同时存在I类和II类HLA-IgG抗体,抗体阳性率>50%的高致敏受者94例。所有受者术后未发生超急性排斥反应,抗体阳性组受者的急性排斥发生率与阴性组受者比较,没有统计学差异。然而抗体阳性组受者移植物功能延迟恢复(DGF)的发生率显著高于阴性组受者(P<0.001)。抗体阳性组受者的1年、3年和5年移植肾存活率分别为95%、88%和80%;与抗体阴性组受者组比较无统计学差异。女性受者中抗体阳性率明显高于男性受者(P<0.001);再次移植受者中抗体阳性率显著高于初次移植受者(P<0.001)。抗体阳性组受者的供受者配型明显优于抗体阴性组受者。HLA-IgG抗体是反映受者体液免疫致敏状态的敏感指标,供受者间良好的HLA配型能显著降低排斥反应发生率和改善移植物存活。     

HLA抗体筛选技术的最新进展及其在器官移植中的应用

人类白细胞抗原(HLA)是介导器官移植排斥反应的主要因素,良好的组织配型是肾移植患者长期存活和术后移植肾功能恢复的重要条件之一。在多次输血、生育史、再次移植的受者受到同种HLA免疫致敏可产生群体反应性抗体(panelreactive antibody,PRA)。PRA是一组特定的人类白细胞抗原(HLA)抗体,有多种类型,包括HLA-A、B、C、DR、DQ等抗体[1],是造成超急性和加速性排斥反应和移植物丢失的危险因素之一。PRA水平的高低更直接地影响移植肾的近期存活率。因此,将抗体筛选技术应用于器官移植实践,对减少移植后排斥反应,提高移植成功率和移植…     

HLA配型和DSA对移植肾功能的影响研究

器官移植中良好的供受者间HLA配型对预防移植肾早期排斥和移植肾的长期存活具有重要意义.肾移植术后发生排斥的重要因素之一是群体反应性抗体(PRA)的参与,特别是肾移植术后产生抗供者特异性抗体(DSA).因此本文对肾移植供受者HLA分型和DSA对移植肾急性排斥反应和近期肾功能进行研究.现报道如下. 材料和方法 一般资料:选择了2007年10月至2009年12月间在我院接受肾移植的128例患者,男性88例,女性40例;最大年龄63岁,最小年龄20岁.     

亲属活体供肾与同期尸体肾移植40例比较

背景:近年亲属活体间肾移植数量明显增加,供肾者的安全性及亲属活体供肾的移植质量受到日益重视。目的:总结40例亲属活体供肾移植的临床经验,评价其效果及安全性。方法:广西中医学院附属瑞康医院移植泌尿外科在2007-06/2008-08共完成亲属活体供肾移植40例,回顾分析供、受者相关的临床资料。同期随机抽取尸肾移植40例,将亲属活体间肾移植受者与尸肾移植受者在血肌酐水平恢复正常时间、急性排斥反应发生率、肾功能延迟恢复发生率、外科相关并发症发生率等方面进行比较。结果:所有供者手术时间仅1.0～2.0h,供肾热缺血时间15s左右,冷缺血时间1.0～2.0h,围手术期间未发生外科及内科并发症。受者术后肾功能恢复快,前3d尿量500～1000mL/h,1周左右血肌酐水平均可降至正常。随访至今,所有供、受者均正常生存,移植肾功能均保持在正常范围。活体肾移植受者在血肌酐水平恢复正常时间、急性排斥反应发生率、肾功能延迟恢复发生率等方面均显著低于尸肾移植。开放切取供肾手术时间短、热缺血时间短,在手术安全性方面也有一定的优势。     

HLA配型、交叉反应组(CREGs)误配率与肾移植术后早期排斥反应的关系

目的：探讨人类白细胞抗原（HLA）配型、交叉反应组（CRECs）误配率与尸体肾移植术后早期急性排斥反应的关系。方法：应用泰萨奇单克隆抗体干板进行供受者HLA-Ⅰ类抗原分型；微量序列特异性引物法进行HLA-Ⅱ类基因分型；泰萨奇混合抗原板检测群体反应性抗体（PRA）。结果：PRA阴性131例肾移植患者HLA配型，误配率为6MM、5MM、4MM、3MM、2MM、1MM、0MM的移植例数分别为0、4、26、49、33、15、4，术后早期急性排斥反应发生率分别为0、25％、23．1％、14．3％、12．1％、6．7％、0。CREGs误配率为6MM、5MM时无移植病例。CREGs误配率为4MM、3MM、2MM、1MM、0MM时，排斥反应发生率分别为28．6％、22．9％、9．5％、6．9％、5．5％。结论：HLA配型、交叉组配型可显著提高供受者的HLA相配率，对选择最佳的供者，降低早期急性排斥反应的发生，提高肾移植效果具有重要的意义。     

夫妻活体供肾移植与血缘亲属供肾移植

背景：夫妻间活体肾移植尽管在组织配型方面差于血缘关系供肾移植,但在临床实践观察中夫妻肾移植与血缘关系肾移植间近期疗效并无明显差异。 目的：对比同期实施的夫妻活体供肾移植和血缘亲属供肾移植的临床疗效,总结夫妻活体供肾移植的临床经验。 方法：回顾性分析郑州人民医院实施的夫妻活体供肾移植18例及血缘亲属供肾移植100例的临床资料,通过对两组移植前组织配型情况和移植后(1,3,6个月)肾功能恢复情况,移植肾功能延迟恢及半年内急性排斥反应发生率、感染发生率等指标的分析,对夫妻活体供肾移植和血缘亲属供肾移植的临床疗效进行比较。 结果与结论：同期进行的18例夫妻活体供肾移植组织配型情况较血缘关属供肾移植患者情况差。在移植方案及免疫抑制治疗方案相同的情况下,夫妻活体供肾移植后6个月内血肌酐恢复情况、术后移植肾功能延迟恢、急性排斥反应发生率、感染发生率,均与同期进行的血缘亲属活体供肾移植差异无显著性意义(P > 0.05)。结果表明,无血缘关系的夫妻间供肾移植与血缘亲属供肾移植治疗效果相近。     

MICA抗体对肾移植患者长期存活影响的初步研究

目前在肾移植术后研究群体反应抗体与移植肾排斥外,主要组织相容性Ⅰ类相关链A抗原(MICA)抗体也处于研究的热点.MICA基因是MIC基因家族的一员,包括MICA、B、C、D、E、F、G这7个成员,MICA距HLA-B位点最近.在某些肾移植术后抗HLA抗体阴性的患者排除细胞性排斥的情况下仍发生急性排斥,甚至亲属肾移植供受者HLA抗原全相配的患者仍发生急性排斥,因此推断可能有其他抗体参与了移植肾排斥.     

应用流式补体依赖淋巴细胞毒技术检测肾移植病人HLA抗体

目的为了更好地识别造成移植肾排斥的特异性抗供者HLA的IgG类型同种抗体，对Flow-CDC方法应用于肾移植及其临床相关性进行研究。方法对96例等候肾移植受者同时进行PRA、NIH-CDC和FloW-CDC实验，并观察其中34例接受NIH-CDC阴性肾移植术的受者近期移植效果。结果FloW-CDC和NIH-CDC两种实验方法的阳性率[27．8％（42／151）和17．3％（26／151）]之间差异有统计学意义（X^2=4．86，P〈0．05）。另外，PRA阴性受者其NIH-CDC和Flow-CDC均为阴性，阴性吻合率为100％；在接受同种异体肾移植术的34例受者，其中20例PRA阴性受者接受了NIH-CDC和Flow-CDC均阴性供肾，移植后未发生排斥，移植肾功能迅速恢复；13例PRA阳性的致敏受者接受NIH-CDC和Flow-CDC均阴性供肾的，1例发生急性排斥经治疗后逆转，12例无排斥移植肾功能良好；1例PaA阳性再次移植受者接受了NIH-CDC阴性而Flow-CDC阳性的供肾，移植后第2天出现少尿，10d切除移植肾。结论Flow-CDC方法是一种能够识别具有补体结合能力的抗供者特异性HLA抗体的交叉配型技术，比经典的NIH-CDC方法具有更敏感、可标准化、快速等优点，对预示肾移植术后的排斥反应方面更具有前瞻性。     

Significance of tumor necrosis factor microsatellite polymorphism in renal transplantation

Plasma levels of tumor necrosis factor (TNF) α are raised during acute rejection following organ transplantation. Variations in TNF á production have been found to be associated with the polymorphism of TNF microsatellite. Therefore, there is a possibility that a transplant recipient with some type of TNF microsatellite can be a high-risk patient of graft rejection. The purpose of this study was to examine whether TNF microsatellite polymorphism is related to acute allograft rejection. We investigated the relation of two microsatellites, TNFa and TNFd, to acute rejection after renal transplantation. Among 189 primary living-related renal transplantations from one haplotype-mismatched and one DRBI-mismatched donor, we analyzed TNF microsatellites of 163 patients whose DNA were available to this study. The frequency of the TNFa9 microsatellite allele was significantly higher in the rejection group compared to the rejection-free group. In contrast, the frequency of TNFd4 was significantly lower in the rejection group compared to the rejection-free group. TNFa9 and TNFd4 showed strong associations with HLA-B35 and B44, respectively. However, the TNF microsatellite locus was more closely related to acute rejection than HLA-B. It was suggested that the analysis of TNF microsatellite polymorphism can provide useful information in predicting prognosis after transplantation.     

Clinical applicability of the immunomagnetic beads technique for serological crossmatching in renal transplantation

ABSTRACT: The aim of the present prospective study was to investigate the clinical applicability of the immunomagnetic (IM) beads technique for serological crossmatching (XM) in renal transplantation. The IM XM were read after various periods of incubation, and the results were compared with those obtained by the conventional Kissmeyer-Nielsen (KN) technique. A total of 132 sera from 96 potential recipients were tested against cells from 62 donors. Eighty-nine KN T-cell XM-negative renal allograft transplantations were performed, and the IM XM results were related to clinical 3-month follow-up data (incidence of primary nonfunction, never functioning grafts, graft losses and rejection episodes). The IM technique was clearly more sensitive than KN, and sensitivity increased markedly with increasing duration of incubation. KN -, IM + reactions were predominantly found among sera from patients with panel-reactive antibodies (PRA, 2p<0.01), and thus probably caused by HLA antibodies. However, positive IM XM, appearing after more than 35 min of incubation, did not influence the overall clinical outcome in the observation period. With reading after exactly 35 min of incubation, XM results obtained by IM and KN techniques correlated well. Thus, we believe, that the IM XM technique will be as safe and effective in avoidance of hyperacute rejections as the conventional assay. In the present material, the incidence of primary nonfunction was significantly (2p = 0.0023) higher among PRA+ recipients compared to PRA - patients. To conclude, we recommended the IM technique with reading after exactly 35 min of incubation for easy, fast (70 min) and reliable XM, that is always possible to perform using peripheral blood.     

Clinical applicability of the immunomagnetic beads technique for serological crossmatching in renal transplantation.

The aim of the present prospective study was to investigate the clinical applicability of the immunomagnetic (IM) beads technique for serological crossmatching (XM) in renal transplantation. The IM XM were read after various periods of incubation, and the results were compared with those obtained by the conventional Kissmeyer-Nielsen (KN) technique. A total of 132 sera from 96 potential recipients were tested against cells from 62 donors. Eight-nine KN T-cell XM-negative renal allograft transplantations were performed, and the IM XM results were related to clinical 3-month follow-up data (incidence of primary non-function, never functioning grafts, graft losses and rejection episodes). The IM technique was clearly more sensitive than KN, and sensitivity increased markedly with increasing duration of incubation. KN-, IM+ reactions were predominantly found among sera from patients with panel-reactive antibodies (PRA, 2p less than 0.01), and thus probably caused by HLA antibodies. However, positive IM XM, appearing after more than 35 min of incubation, did not influence the overall clinical outcome in the observation period. With reading after exactly 35 min of incubation, XM results obtained by IM and KN techniques correlated well. Thus, we believe, that the IM XM technique will be as safe and effective in avoidance of hyperacute rejections as the conventional assay. In the present material, the incidence of primary nonfunction was significantly (2p = 0.0023) higher among PRA+ recipients compared to PRA- patients. To conclude, we recommended the IM technique with reading after exactly 35 min of incubation for easy, fast (70 min) and reliable XM, that is always possible to perform using peripheral blood.     

HLA mismatching and cytomegalovirus infection as risk factors for transplant failure in cyclosporin-treated renal allograft recipients

In a study of the effects on renal allograft survival of HLA mismatching, mismatching for cytomegalovirus (CMV) antibody status, and post-transplant CMV infection, 148 cyclosporin-treated renal transplant recipients were given kidneys optimally matched for HLA-A, -B, and -DR antigens but not matched for CMV antibody status. Mismatching for HLA-B and -DR antigens was associated with a greater number of rejection episodes and a lower graft survival, but mismatching for CMV antibody status and posttransplant primary or recurrent CMV infection exerted no effect on graft survival. The role of matching of renal transplant recipients and donors for CMV antibody status in preference to HLA matching (proposed as a means of reducing the mortality associated with primary CMV infection) is discussed.     

Lymphocytotoxic cross-matching performed on spleen cells: immunomagnetic technique versus current KN (Kissmeyer-Nielsen) technique

This paper compares the immunomagnetic (IM) and the KN lymphocytotoxic cross-matching techniques. Only sera from patients with panel reactive antibodies and spleen cells from cadaveric donors were used. A panel study involving 60 combinations revealed 11 (18%) discrepancies. Four T-cell cross-matches were KN negative while IM positive. Inversely, six T-cell cross-matches were IM negative while KN positive (two) or doubtfully positive (four). Regarding HLA class II antibodies, one combination was found IM positive but KN negative. Out of 106 cadaveric renal allograft transplantations performed during 1987 with assistance from our laboratory, IM cross-matching was retrospectively performed on 33 KN T-cell cross-match negative donor-recipient pairs: two combinations were found T-cell cross-match positive. The corresponding allografts were not lost owing to hyperacute rejection involving performed antibodies. We recommend the IM technique for HLA typing, but more experience needs to be gained before we can recommend the technique for routine cross-matching prior to transplantation.     

TNF-alpha and TGF-beta1 gene polymorphisms and renal allograft rejection in Koreans

This study was performed in order to evaluate the association of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) gene polymorphisms with renal allograft rejection in Koreans. Five TNF-alpha (-1031T/C, -863C/A, -857C/T, -308G/A and -238G/A) and two TGF-beta1 (codon 10 T/C and codon 25 G/C) single-nucleotide polymorphism (SNP) sites were studied by using polymerase chain reaction (PCR) single-strand conformation polymorphism and PCR restriction fragment length polymorphism methods in 100 controls and 164 patients. The patients underwent renal transplantation, having one or more Human leukocyte antigen (HLA)-A, HLA-B and HLA-DR antigens mismatched with their donors. For the TGF-beta1 gene, we also studied the polymorphism of donors. The allele frequencies of each SNP site in controls were not different from those of patients. The frequency of TNF-alpha high-producer genotype, -308GA, and TGF-beta1 lower (intermediate)-producer genotype, codon 10 CC and codon 25 GG, were significantly higher in patients with recurrent acute rejection episodes (REs), compared to those in patients with no or one RE. The highest risk group for developing recurrent REs showed the combination of TNF-alpha high- and TGF-beta1 lower-producer genotypes. Analysis of chronic renal allograft dysfunction (CRAD) revealed that TGF-beta1 high-producer genotype of donors, codon 10 TT/TC and codon 25 GG, is associated with CRAD especially in patients with recurrent REs. The highest risk group for developing CRAD showed the combination of recipient's TNF-alpha high- and donor's TGF-beta1 high-producer genotypes. These results would be useful for predicting high-risk group for acute rejection or CRAD in renal transplantation.     

肾移植受者血清sFas和sFasL变化及在早期急性排异反应预测中的应用

背景：细胞凋亡在移植免疫和移植物功能丧失发生过程中起十分重要的作用,其中Fas/FasL系统被认为是细胞凋亡参与肾移植的急性排异反应过程的主要途径之一。 目的：分析肾移植受者术后血清sFas和sFasL水平变化及其在预测早期急性排异反应中的应用价值。 方法：肾移植受者80例分为肾功能稳定组(49例)、急性排斥反应组(23例)和环孢素A中毒组(8例)。另选择性别、年龄与肾移植受者相匹配的健康体检者50例为对照组。肾移植受者术后均常规使用环孢素A+硫唑嘌呤+泼尼松三联免疫抑制治疗。发生急性排斥反应时给予每日甲基强的松龙6~8 mg/kg冲击治疗,3 d为1个疗程。采用ELISA法检测患者手术前后的血清sFas和sFasL水平。 结果与结论：肾移植组患者手术前的血清sFas和sFasL水平均明显高于对照组(P  < 0.05)。急性排斥反应组血清sFas、sFasL水平高于相同时间段肾功能稳定组(P < 0.05)。环孢素A中毒的肾移植患者术后各时间点血清sFas、sFasL水平变化与肾功能稳定组基本相同,差异无显著性意义。提示动态监测血清sFas、sFasL水平可能对早期诊断及鉴别诊断肾移植急性排斥反应具有重要参考价值。     

供者特异性活化T细胞频度预测肾移植急性排斥反应

背景：提高移植后排斥反应风险预报的准确性,可为移植后个体化使用免疫抑制剂提供参考。 目的：寻找一种能定量分析供受者间免疫反应强度的方法来预测急性排斥反应。 方法：对同种异体尸肾移植的患者115例采用前瞻性分析,用ELISPOT法检测移植前分泌γ-干扰素的供者特异性活化T细胞的频度,观察随访期内有无急性排斥及肺部感染,并观察HLA错配与急性排斥的关系。 结果与结论：115例群体反应性抗体阴性肾移植受者中有25例发生急性排斥反应,发生急性排斥反应患者的供者特异性活化T细胞频度高于未发生急性排斥反应者(P < 0.01),而HLA-I、II及总的错配数比较,差异均无显著性意义(P > 0.05)。提示,通过移植前对产生γ-干扰素的供者特异性活化T细胞频度的检测,可预测急性排斥反应,对潜在供者进行选择。     

丹参注射液在肾移植后急慢性排斥反应中的作用

背景：临床观察,肾移植后发生急、慢性排斥反应时单用甲基强的松龙针冲击,尿蛋白、血肌酐值改善不明显,若加用丹参注射液静脉滴注,可使移植肾功能恢复更迅速。 目的：观察丹参注射液对肾移植后急慢性排斥反应肾功能恢复的影响。 方法：肾移植后发生急性排斥反应患者180例,慢性排斥反应患者140例,分别随机分成两组,对照组单纯应用常规甲基强的松龙冲击治疗3 d,治疗组在此基础上加用丹参注射液静脉滴注15 d。 结果与结论：与治疗前相比,急慢性排斥反应两组肾功能恢复指标均有明显改善,差异有显著性意义(P < 0.05);治疗组比对照组肾功能指标改善更明显(P < 0.05)。且治疗组延长了凝血酶原时间和活化部分凝血活酶时间(P < 0.05)。结果证实了肾移植患者发生急慢性排斥反应后在常规处理基础上加用丹参注射液能明显改善移植肾功能。     

Decreased humoral antibody episodes of acute renal allograft rejection in recipients expressing the HLA-DQβ1*0202 allele

The present investigation was designed to show the effect of human leukocyte antigen (HLA) class II molecular allelic specificities in the recipient on the induction of humoral antibody rejection, identified by C4d peritubular capillary staining, as well as specific antibody identified by Luminex technology. Major histocompatibility complex (MHC) class II molecules are expressed on dendritic cells, macrophages, and B lymphocytes and they present antigenic peptides to CD4 positive T lymphocytes. Human renal peritubular and glomerular capillaries express class II MHC molecules upon activation. Expression of class II molecules on renal microvascular endothelial cells exposes them to possible interaction with specific circulating antibodies. We hypothesize that HLA-DQβ1*0202 expression in recipients decreases the likelihood of antibody-mediated renal allograft rejection. We found that 80% (=25) of DQ2 positive haplotype recipients failed to induce humoral antibody renal allograft rejection and 20% (n=25) of DQ2 positive haplotype recipients induced humoral antibody renal allograft rejection (p=0.008). By contrast, 48% (n=46) of DQ2 negative haplotype recipients failed to induce a humoral antibody component of renal allograft rejection and 52% (n=46) of DQ2 negative haplotype recipients induced humoral antibody-mediated renal allograft rejection. Our results suggest that recipients who express the DQβ1*0202 allele are less likely to induce a humoral antibody component of acute renal allograft rejection than are those expressing DQ1, DQ3, or DQ4 alleles. DQβ1*0202 allele expression in recipients could possibly be protective against acute humoral allograft rejection and might serve as a future criterion in recipient selection and in appropriate therapy for acute renal rejection episodes.