无血缘夫妻活体供肾7例肾移植

背景：通过诱导移植受体产生供-受体嵌合体或免疫耐受以利于受体长期存活,一直是器官移植的研究热点,并且在实验动物模型中获得了大量成功的经验和知识。在临床实践中也观察到结婚多年的夫妻,丈夫-妻子器官移植后排斥反应小,具有比其他的亲属器官移植有更多的优点。 目的：回顾性分析无血缘关系的活体供肾移植—丈夫对妻子供肾移植的临床效果。 方法：选择7例夫供妻活体肾移植,供者年龄 32~58岁,受者年龄 31~56岁,双方婚龄在5~36年。供、受者 ABO血型完全相同者 4例,O-B 1例,O-A 1例,A-AB型 1例。淋巴细胞毒交叉配合试验阴性。HLA配型情况：1个抗原错配 1例,2个抗原错配 2例,3个抗原错配3例,4抗原错配 1例。开放手术取肾,6例左肾,1例右肾。术后采用三联免疫抑制方案：环孢素A/他克莫司+麦考酚酸吗乙酯+泼尼松预防排斥反应,7对供受者随访3~70个月。 结果与结论：手术成功率100%,供受者均未发生手术相关并发症,所有供者血压、尿常规及肾功正常,受者及移植肾全部存活。验证了虽然移植前组织配型结果较差,但由于夫妻间长期生活在一起产生的免疫耐受,使夫供妻肾移植后排斥反应小、移植效果理想,具有比其他的亲属肾移植有更多的优点。     

HLA致敏性错配对肾移植受者急性排斥反应发生率的影响

目的　探讨供受者HLA致敏原性错配(IM)对肾移植受者急性排斥反应发生率的影响。方法　回顾性分析196例首次肾移植受者IM对肾移植术后肾功能恢复时间及1年内排斥反应发生率的影响。结果　IM对肾移植术后肾功能恢复时间无明显影响;IM患者1年内急性排斥反应发生率明显增加,各类位点IM对肾移植术后急性排斥的影响比较,A位点影响不大,B位点与急性排斥有关,DR位点IM可致急性排斥明显增加。结论　在临床采用HLA氨基酸残基配型标准判断组织配型的同时,IM不容忽视,HLA B位点IM与肾移植术后急性排斥反应相关,HLA DR位点IM明显影响肾移植术后急性排斥反应发生率。     

肾移植术后早期急性排斥反应与急性肾小管坏死的鉴别诊断及护理

急性排斥反应和急性肾小管坏死都是肾移植术后常见并发症,两者术后都是以少尿、无尿为主要特点,术后早期较难鉴别。我科从1998年11月至2005年6月共进行同种异体肾移植术268例,其中发生急性排斥反应30例,发生率为11.19%;急性肾小管坏死27例,发生率为10.07%,现报告如下。1临床资料本组268例肾移植术患者中,发生急性排斥反应30例,男性17例,女性13例,年龄9~68岁,经用甲基强的松龙冲击治疗及OKT3、ATG、ALG等治疗,26例逆转,1例因移植肾自发性破裂而摘除,3例移植肾;发生急性肾小管坏死27例,男性12例,女性15例,年龄28~69岁,经透析治疗后25例均…     

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。     

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。     

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.     

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…     

趋化因子受体多态性与肾移植临床结果的关系

目的：探讨趋化因子受体CCR5-59029、CCR2-64I多态性与肾移植临床结果的关系。方法：应用PCR限制性片段长度多态性分析方法（PCR-RFLP）检测72例同种异体肾移植病人CCR5-59029、CCR2-64I基因多态性，并分析两个等位基因多态性与急性排斥反应和存活时间的关系。结果：本组16例发生急性排斥反应。25例CCR5-59029A／A基因型受者，9例发生急性排斥反应，排斥反应发生率明显增高。具有CCR2-64I基因型受者，急性排斥反应发生率无明显变化。CCR2-64I基因型受者平均存活时间长于非此基因型受者。结论：趋化因子CCR5-59029A／A基因型是急性排斥反应的高危因素。CCR2-64I与肾移植术后长期存活相关。     

肾移植排斥反应时机体止血功能的变化

肾移植是目前治疗终末期肾病最理想的办法,但是排斥反应仍然是导致移植肾功能丧失及病人死亡的主要并发症之一。本课题从血小板、凝血与抗凝和纤溶３个方面对１１例（次）肾移植急性排斥反应治疗前和症状控制后进行了观测,以了解肾移植急性排斥反应时机体止血功能的变化,并对其在急性排斥反应病理机制中的作用进行探讨。资　料　和　方　法一、观察对象：１８例同种异体肾移植,男１４例,女４例,年龄（４３±８－８）岁,出现急性排斥反应（诊断：发热、少尿、移植肾区触痛、血肌酐升高以及Ｂ超和病理改变）共１１例（次）。血样品采集…     

肾移植急性排斥反应时B7-2/CD28信号通路的表达*☆

背景：以往动物研究表明,在器官移植急性排斥反应时共刺激分子的表达与急性排斥反应密切相关。 目的：观察急性排斥反应时患者移植肾脏组织和外周血中B7-2/CD28信号通路的表达。 方法：对53例同种异体肾移植患者于移植前1 d、移植后1,3,7,14,21,28 d分别取外周血以及在临床诊断急性排斥反应当天和抗排斥治疗1周后额外采血,用流式细胞仪检测共刺激分子B7-2/CD28在外周血淋巴细胞中的表达;同时,行经皮肾穿刺活检供肾修整结束时、移植后7 d、1个月、6个月、1年或以上获取活检肾脏组织,用免疫组织化学方法检测活检组织中B7-2/CD28的表达情况。 结果与结论：移植后1,3 d内所有患者外周血中CD28+,CD4+/CD28+,CD8+/CD28+细胞比率均有显著下降(P < 0.05),一二周后恢复到术前水平;移植后7 d未发生急性排斥反应的患者肾脏组织B7-2阳性表达率显著上升(P < 0.05),1个月后下降至移植前水平(P > 0.05)。移植后发生急性排斥反应的患者外周血CD28+,CD4+/CD28+,CD8+/CD28+细胞比率及肾脏组织B7-2阳性表达率明显上升(P < 0.05),经抗排斥治疗1周后均好转。结果证实,在肾移植后出现急性排斥反应时,肾脏组织以及外周血中共刺激分子B7-2/CD28的表达上调与急性排斥反应的发生密切相关。       

Neutrophils mediate parenchymal tissue necrosis and accelerate the rejection of complete major histocompatibility complex-disparate cardiac allografts in the absence of interferon-gamma

A major feature of acute rejection of cardiac allografts is an intense mononuclear cell infiltration accompanied by interferon (IFN)-gamma production. In the current study we tested the role of IFN-gamma in acute rejection of allografts by comparing the histopathology of rejection in wild-type versus IFN-gamma-/- recipients of major histocompatibility complex-mismatched cardiac grafts. Wild-type recipients rejected the allografts at days 8 to 9 after transplant but rejection was accelerated 2 to 3 days in IFN-gamma-deficient recipients. During rejection in wild-type recipients, the allografts were heavily infiltrated with CD8+ T cells and other mononuclear cells. In contrast, allografts in IFN-gamma-deficient recipients had few T cells but an intense neutrophil infiltration accompanied by extensive graft parenchymal necrosis. No difference in expression levels of neutrophil chemoattractants including Groalpha/KC, MIP-2, GCP-2, and MIP-1alpha, was observed in allografts retrieved from wild-type and IFN-gamma-/- recipients. Depletion of neutrophils from IFN-gamma-deficient recipients delayed rejection until days 8 to 10 after transplant and restored the histopathology of acute allograft rejection to that observed in allografts rejected by wild-type recipients. These results indicate the potent regulatory properties of IFN-gamma during acute rejection directed at neutrophil infiltration into allografts and mediating graft tissue necrosis.     

CD40靶向小干扰RNA抑制大鼠异体肢体移植急性排斥反应后细胞凋亡及P53、P21表达

目的探讨CD40靶向小干扰RNA（即短发夹RNA，shRNA）对大鼠异体肢体移植急性排斥反应及细胞凋亡的影响。方法以纯系SD大鼠为供体，纯系Wistar大鼠为受体，行同种异体右后肢移植。27只大鼠肢体移植后随机分为3组：实验组．注射梭华一Sofast（15μl）-siCD40—2，pSilencer（100μg）载体复合物600μl；空载体对照组，在肢体移植后，即注射Sofast（15μl）-pSilencer4．1-CMVneo（100μg）空载体复合物600μl；生理盐水对照组，在肢体移植注射生理盐水600μl。观察移植物排斥反应征象及存活情况，并于第7天对产生免疫耐受大鼠进行混合淋巴细胞反应（MLR），同时进行组织学检查。结果与其他组相比．实验组移植物发生排斥反应的时间及存活时间均显著延长（P〈0．01）（〉13d），未见排斥反应征象，其他组均于术后近期发生排斥反应；实验组大鼠对供体的淋巴细胞呈现低反应性，移植的供体同系大鼠的肢体得以存活。实验组移植物细胞凋亡率低于其他组。结论在术后不应用免疫抑制剂的情况下，CD40靶向的shRNA干扰可以抗大鼠异体肢体移植急性排斥反应。     

献血者ABO血型反定型O细胞凝集原因分析

目的分析献血者ABO血型反定型O细胞凝集原因,以确保受血者输血安全。方法对江门市2000年1月至2008年6月间,采用微板法检测献血者ABO血型出现反定型O细胞凝集者进行冷凝集素效价测定、吸收放散试验、意外抗体鉴定等血型血清学检测。结果308410例献血者中有25例出现反定型O细胞凝集。其中血清中含有冷凝集素导致O细胞凝集16例：效价1：4～1：32者10例、效价≥1：64者6例：血清中存在意外抗体导致O细胞凝集9例：抗-M（IgM）5例、抗-Le^a（IgM）2例、抗-Le^b（IgM）1例、抗-P1（IgM）1例。结论采用微板法检测献血者ABO血型出现反定型O细胞凝集时,应进行相关的血型血清学检测;非血源紧缺的情况下,反定型O细胞凝集者不宜作为献血者。     

Influence of recipient and donor IL-1alpha, IL-4, and TNFalpha genotypes on the incidence of acute renal allograft rejection

AIMS: To determine whether polymorphisms of the genes encoding donor or recipient interleukin 1alpha (IL-1alpha), tumour necrosis factor alpha (TNFalpha), or IL-4 have any impact on the incidence of acute rejection after renal transplantation. METHODS: All donors and recipients were genotyped for three polymorphisms in the three cytokine genes: IL1A -889, TNFA -308, and IL4 -590. RESULTS: Statistical analysis of the data obtained revealed no association between the cytokine gene polymorphisms tested and the incidence of post-transplant acute rejection. After stratification for human leucocyte antigen (HLA) matching, it was found that kidneys from donors positive for the TNFA-A allele had a significantly increased incidence of acute rejection in HLA-DR mismatched transplants. CONCLUSIONS: This finding argues for prospective TNFA genotyping of renal donors, with avoidance of allocation of kidneys from donors positive for the TNFA-A allele to HLA-DR mismatched recipients.     

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。     

Significance of histocompatibility tests

Pretransplant tests necessary for kidney transplantation are HLA typing, mixed lymphocyte culture response (MLR), and direct crossmatch. HLA typing and MLR are closely related to graft survival rates. The significance of HLA matching is generally known. In our analysis of 25 living related kidney grafts, graft survival rate of two haplo identical donor transplants was 4/4 (100%), while that of one haplo identical donor transplant was 18/21 (85.7%). Acute rejection rate in the MLR low response group (S.I. less than or equal to 5) was 2/7 (28.6%), while that in the high response group (S.I. greater than 5) was 11/19 (57.9%). HLA typing and MLR are useful in selecting the most suitable recipient. In order to reduce the risk of hyperacute or accelerated graft rejection, T warm direct crossmatch is performed. Anti-T warm antibodies are mainly produced by blood transfusion. In our study of 239 hemodialysis patients, there were 31 patients with positive T warm (13.0%), the positive rate became higher in proportion to increases in blood transfusion. Recently, there have been reports of kidney transplants successfully performed across T warm-positive crossmatches due to IgM antibodies. We also investigated the immunoglobulin class. Not only pretransplant crossmatch but also posttransplant crossmatch is necessary. In the case of accelerated, acute or chronic rejection, anti-donor HLA antibodies are produced in patients' peripheral blood. Thus, the test of posttransplant anti-donor antibodies is useful for the early detection of rejection, its diagnosis, and index of the prognosis. The sensitivity of flow cytometry crossmatches was compared to standard cytotoxicity crossmatch. Titration studies indicate a 32-64 fold range of greater sensitivity than the cytotoxicity test.(ABSTRACT TRUNCATED AT 250 WORDS)     

胚胎卵巢移植的免疫学研究

目的：探讨在胚胎卵巢移植中,组织抗原的配型、受体的免疫学反应及 其卵巢存活,发育、功能和治疗前景的关系。方法：分别以血清学和PCR－SSP方法进行供、受体的HLA－A、B和DR抗原分型,以ELISA方法测定术后受体血清中抗卵巢抗体,以B超监测卵巢和以放射免疫方法测定受体血清中FSH、LH、E2和P的水平。结果：供、受体之间至少2个HLA抗原位点相同,移植的4例卵巢全部存活,卵巢发育良好,FSH、LH水平下降,E2、P水平上升,但2例受体血清抗卵巢抗体阳性,结论：胚胎卵巢移植有较好的前景。     

Influence of HLA disparity, immunosuppressive regimen used, and type of kidney allograft on production of anti-HLA class-I antibodies after transplant and occurrence of rejection

We studied the effects of HLA disparity, immunosuppressive regimen used, and the type of kidney allograft on production of anti-HLA antibodies after transplant and the occurrence of rejection episodes. Five living-unrelated donors and 4 living-related donors kidney recipients received quadruple therapy (including sirolimus and mycophenolate mofetil). Fifteen living-unrelated donors and 19 living-related donors received triple therapy (excluding sirolimus). A single bolus of 4 to 6 mg/kg rabbit anti-human T-lymphocyte immune serum was included with both regimens. Recipients were studied over a 3-year period. Human leukocyte antigen profiles were determined by DNA (SSP) typing, and anti-HLA class-I antibodies were determined by the complement-dependent microcytotoxicity assay and an enzyme-linked immunosorbent assay. The degree of HLA disparity did not appear to affect anti-HLA antibody production or the occurrences of rejection episodes. None of the patients who received quadruple therapy developed anti-HLA class-I antibodies. Two living-unrelated donors and 2 living-related donors recipients who received triple therapy developed anti-HLA class-I antibodies. One of the 2 living-unrelated donors antibody-positive patients rejected the kidney and returned to dialysis, and the other patient has normal graft function 3 years after the transplant. The 2 living-related donors patients with normal graft function were antibody-positive 1 year after the transplant but were antibody-negative at 2 and 3 years after transplant. Sirolimus appeared to inhibit production of antibodies after transplant. Moreover, use of present day immunosuppressive agents diminishes the role of HLA matching in relation to the occurrence of rejection episodes.     

Influence of HLA disparity,immunosuppressive regimen used,and type of kidney allograft on production of anti-HLA class-I antibodies after transplant and occurrence of rejection

We studied the effects of HLA disparity, immunosuppressive regimen used, and the type of kidney allograft on production of anti-HLA antibodies after transplant and the occurrence of rejection episodes.

Five living-unrelated donors and 4 living-related donors kidney recipients received quadruple therapy (including sirolimus and mycophenolate mofetil). Fifteen living-unrelated donors and 19 living-related donors received triple therapy (excluding sirolimus). A single bolus of 4 to 6 mg/kg rabbit anti-human T-lymphocyte immune serum was included with both regimens. Recipients were studied over a 3-year period. Human leukocyte antigen profiles were determined by DNA (SSP) typing, and anti-HLA class-I antibodies were determined by the complement-dependent microcytotoxicity assay and an enzyme-linked immunosorbent assay.

The degree of HLA disparity did not appear to affect anti-HLA antibody production or the occurrences of rejection episodes. None of the patients who received quadruple therapy developed anti-HLA class-I antibodies. Two living-unrelated donors and 2 living-related donors recipients who received triple therapy developed anti-HLA class-I antibodies. One of the 2 living-unrelated donors antibody-positive patients rejected the kidney and returned to dialysis, and the other patient has normal graft function 3 years after the transplant. The 2 living-related donors patients with normal graft function were antibody-positive 1 year after the transplant but were antibody-negative at 2 and 3 years after transplant.

Sirolimus appeared to inhibit production of antibodies after transplant. Moreover, use of present day immunosuppressive agents diminishes the role of HLA matching in relation to the occurrence of rejection episodes.