肾移植术后排斥反应与巨细胞病毒感染有关

目的 :探讨巨细胞病毒 (CMV)感染在肾移植术后的发生率及CMV感染与排斥反应的关系。方法 :检测2 0 8例肾移植受者术后CMVDNA和 48例肾移植受者血清CMVIgM、IgG抗体。并定期复查CMVDNA ,对CMVDNA阳性的患者给予抗病毒治疗。结果 :术后CMVDNA阳性受者急性排斥反应的发生率增加 ,经抗CMV治疗 ,则排斥反应减少。结论 :预防和治疗CMV感染的重要性     

肾移植术后巨细胞病毒感染与急性排斥反应

目的 :探讨肾移植术后活动性巨细胞病毒 (CMV)感染的发生率、原因以及对急性排斥反应的影响。方法 :检测 182例肾移植受者及其供者术前血清抗CMV抗体 ,受者术后定期PCR法检测体内CMVDNA ,对CMVDNA阳性的部分患者给予抗CMV治疗 ,并比较各组排斥反应的发生率。结果 :无论是供者还是受者 ,术前如血清抗CMV抗体阳性 ,受者术后发生活动性CMV感染者明显增多 ,且急性排斥反应的发生率亦明显增加 ;接受抗病毒治疗急性排斥反应明显减少。结论 :CMV感染是肾移植术后急性排斥反应的原因之一 ,预防和治疗CMV感染对肾移植术后急性排斥反应的防治具有重要意义。     

肾移植受者巨细胞病毒感染与抗心磷脂抗体的关系

目的：探讨肾移植受者巨细胞病毒（cytomegalovirus,CMV)感染与抗心磷脂抗体（anticardiolipin antibody,ACA)产生的关系。方法：肾移植受者146例术后采用定性聚合酶链反应（PCR）检测CMV－DNA，同时用酶 联免疫吸附法（ELISA）检测血清抗心磷脂抗体免疫球蛋白G（ACA-IgG），并与正常对照组（n=32)进行比较。结果：肾移植受者146例ACA阳性率为17．1％，与正常对照（6．3％）无明显差异；而CMV感染的肾移植受者ACA阳性率为31．2％，显著高于未感染CMV的受者（7．1％）及正常对照组（6．3％，P＜0．01）。结论：肾移植受者ACA的产生与CMV感染密切相关，可能是CMV导致移植肾慢性血管病变的原因之一。     

术前巨细胞病毒感染对肾移植的影响

目的探讨术前巨细胞病毒(cytomegalovirus infection,CMV)感染对肾移植术后急性排斥反应(acute rejection,AR)的影响及术前预防性抗病毒治疗的意义.方法回顾性分析了116例肾移植受体的术前CMV感染和预防性抗病毒治疗情况,根据术前有无CMV感染分为感染组和非感染组,将CMV感染组肾移植受体根据有无预防性抗病毒治疗分为治疗组和非治疗组.同时检测35例正常健康者CMV结果.采用检测CMV-PP65抗原诊断CMV感染.结果术前CMV感染率肾移植受体为63.8%(74/116)高于正常健康者14.3%(5/35).术后发生CMV感染或CMV病非治疗组为5例(15.6%)高于治疗组1例(2.4%).发生急性排斥反应的术前CMV感染组为14例(18.9%)高于非感染组2例(4.8%).术后发生AR治疗组为4例(9.5%)低于非治疗组10例(31.3%).结论肾移植受体术前CMV感染发生率高于正常健康人群.预防性抗病毒治疗可以降低术后CMV感染或CMV病的发生率.术前CMV感染的肾移植受体术后AR发生率高于非感染者.对术前CMV感染患者采取预防性抗病毒治疗可以降低术后AR的发生率.     

造血干细胞移植后患者血浆巨细胞病毒DNA拷贝数与巨细胞病毒病的关系

目的 评价实时定量聚合酶链式反应(RQ-PCR)法监测造血干细胞移植后患者血浆巨细胞病毒(CMV)DNA水平的临床意义.方法 对2005年1月至2007年1月之间进行异基因造血干细胞移植的318例患者,自移植应采用RQ-PCR每周监测血浆CMV-DNA水平,6×102拷贝/ml视为CMV-PCR阳性.结果 共136例患者(42.8%)检测出1025例次血浆CMV-DNA阳性,首次阳性出现的中位时间为42 d,最高拷贝数及初始拷贝数中位值分别为1.5×104拷贝/ml和4.5×103拷贝/ml.318例患者中共发生CMV肺炎及肠炎23例,累积发病率为7.2%.14例患者在发生CMV病之前出现CMV血症,4例在出现临床表现后方检测出病毒阳性,另有5例CMV血症阴性的患者诊断为CMV疾病.发生CMV病的患者其CMV-DNA最高拷贝数高于未发生组患者(4.3×104拷贝/ml比1.3×104拷贝/ml,P=0.009),但初始拷贝数差异无统计学意义(3.7×103拷贝/ml比4.7×103拷贝/ml,P=0.63).CMV-DNA最高拷贝数随着发生CMV感染的次数增加而增高,在发生CMV感染1～4次的患者中,中位数值分别为82.6×102、261.3×102、440.8×102和10 659.0×102拷贝/ml(P<0.01),且CMV肺炎及CMV肠炎发病率也从2.7%(5/182)明显上升至50%(2/4)(P=0.001).结论 采用RQ-PCR法监测造血干细胞移植后患者血浆CMV-DNA水平对CMV病的发生有一定的预测意义,高CMV-DNA拷贝数及多次感染者预示着CMV病发生概率升高.     

Reinfection of cytomegalovirus in renal transplantation

Cytomegalovirus (CMV) is the most important pathogen affecting the outcome of renal transplantation. Reinfection of CMV can occur in CMV-seropositive donors and CMV seropositive recipients (D+/R+) settings because the protection against CMV conferred by preexisting immunity is limited due to its strain-dependent immune responses. To analyze the influence of CMV reinfection in renal transplantation, ELISA using fusion proteins encompassing epitope of glycoprotein H(gH) from both AD169 and Towne strains was employed before transplantation. The CMV-gH seropositive rate increased with increases in age and the rate of samples which contained antibodies against both AD169 and Towne were significantly high in the age of 50 years or over. Antibodies from HLA-DR10 and DR11 were associated with a significantly lower response rate against CMV-gH. In renal transplantation, the high degrees of antigenemia and high incidences of CMV disease are more prevalent in the CMV gH antibody-mismatched group in D+/R+ setting. The nucleotide sequence of the region of the gH epitope in the CMV-DNA extracted from the transplant recipients who showed high degree of antigenemia revealed the CMV reinfection from the donors. As a CMV indirect effect, the incidence of acute rejection in the mismatched gH antibody group was higher than that observed in the matched and D+/R- groups. The adverse events were more likely to occur in cases of D+/R+ renal transplantation with mismatched strain-specific antibodies which would indicates the risk of CMV reinfection after transplantation.     

Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis

We studied the effects of cytomegalovirus (CMV) infection on 301 cardiac transplant recipients who were treated during the cyclosporine era of immunosuppression (1980 to the present). These patients received varying combinations of cyclosporine, azathioprine, prednisone, rabbit antithymocyte globulin, and OKT3 as their immunosuppressive therapy. Two hundred ten patients were free of CMV infection (non-CMV group). During the same period CMV infection developed in 91 patients, as manifested by a fourfold IgG serologic titer rise, demonstration of CMV inclusion bodies in tissue, or positive cultures for the virus (CMV group). The rate of graft rejection was significantly higher in the CMV group. Graft atherosclerosis was significantly more severe in the CMV group as judged by angiographic criteria or by pathologic study. Patient survival rates were significantly lower in the CMV group. Death caused by graft atherosclerosis was significantly more common among patients in the CMV group. Finally, the graft loss rate (from either death or retransplantation for atherosclerosis) was significantly greater in the CMV group. These data demonstrate that CMV infection in cardiac transplant recipients is associated with more frequent rejection, graft atherosclerosis, and death.     

糖尿病视网膜病变患者巨细胞病毒检测及临床意义

目的 探讨巨细胞病毒(CMV)感染与糖尿病视网膜病变(DR)的关系.方法 采用聚合酶链反应(PCR)技术分别检测各组患者CMV-DNA,结果做统计学处理.糖尿病(DM)组76例,包括无视网膜病变(NDR)组30例、单纯性视网膜病变(也称为背景型视网膜病变,BDR)组29例、增殖性视网膜病变(PDR)组17例;正常对照组(NC)30例.结果 DM组CMV-DNA检测阳性率(51.31%)明显高于NC组(13.33%),DM组中PDR组阳性率(76.47%)高于BDR组(58.62%)和NDR组(30.00%).结论 CMV感染与糖尿病视网膜病变的发生有关,CMV感染可加重糖尿病视网膜病变.     

Cytomegalovirus infection as a complication of OKT3 therapy in kidney transplant recipients

We compared the incidence of clinical CMV illness in 25 renal transplant recipients treated with OKT3 for steroid resistant cellular rejection with 88 renal transplant patients treated only with conventional immunosuppression (cyclosporin A and steroids). Nine (36%) patients in the OKT3 group developed CMV illness compared to (2.3%) amongst those treated conventionally (p<0.0005). Patients who received OKT3 were divided into four groups according to the CMV antibody status of the donor and recipient. Six of the 9 episodes of CMV infection occurred in patients not previously exposed to CMV, who received a kidney from a CMV positive donor. Three (12%) of the patients treated with OKT3 died of CMV disease. A further 2 patients died of other causes giving an overall mortality in the OKT3 treated group of 20%. We concluded that when OKT3 therapy is used in association with donor/recipient CMV mismatch it is associated with a high CMV morbidity and mortality.     

肾移植术后巨细胞病毒检测的临床意义

目的　探讨肾移植术后检测巨细胞病毒感染的意义。方法　利用酶联免疫吸附法 (Enzymelinkedimmunosor bentassay ,ELISA)以及聚合酶链反应 (Polymerasechainreaction ,PCR)检测肾移植术后受者血清中的抗 CMV抗体及CMV DNA。结果　检测了 72例肾移植术后的受者抗 CMV抗体及CMV DNA ,抗 CMV抗体及CMV DNA阳性率均明显高于术前(P <0 0 1) ,其中 2 5 %的CMV感染者发展为CMV病。移植术后CMV DNA阳性者发生急性排斥反应的几率明显高于CMV DNA阴性者。结论　检测肾移植受者血清中的抗 CMV抗体及CMV DNA可以协助诊断肾移植受者是否感染CMV以及引起的CMV病 ,对临床治疗肾移植术后CMV病有着重要的意义     

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。     

2剂赛尼哌预防肾移植术后急性排斥反应的应用研究

目的 :探讨赛尼哌在预防同种肾异体移植术后急性排斥反应的作用。方法 :回顾分析了已随访 1年的 32例应用 2剂赛尼哌患者的临床效果 ,并以同期肾移植 92例作为对照组。结果 :赛尼哌组在 3月内急性排斥反应发生率 (3.1% )显著低于对照组 (2 3.9% ) (P <0 .0 5 ) ,在感染及副作用方面与对照组无显著性差异。结论 :2剂赛尼哌加上CsA ,MMP ,Pred联合应用的免疫抑制方案对预防同种尸体肾移植受者的急性排斥反应的发生是安全有效的。     

造血干细胞移植后巨细胞病毒感染临床分析

目的观察各种类型的造血干细胞移植（HSCT）后巨细胞病毒（CMV）感染的发生情况及疗效。方法选择我院59例异基因造血干细胞移植（allo—HSCT）和自体造血干细胞移植（auto—HSCT）患者移植后不同时期血和尿标本，检测CMV—pp65抗原及（或）CMV—DNA（荧光定量PCR法）进行动态观察分析。CMV感染的预防采用更昔洛书（DHPC）5～10mg／kg，1次／12h，分别在移植前第8天至移植当天及当CMV血清学检测阳性或发生CMV病时应用2-4周，并可同时应用大剂量丙种球蛋白。结果CMV感染在allo—HSCT后好发，非亲缘性移植CMV感染率高，9例allo—HSCT出现CMV感染发生在移植后＋42-＋68天，其中5例均存在不同程度的移植物抗宿主病（GVHD），尤其是Ⅱ～Ⅳ度急性GVHD，2例进展为巨细胞间质性肺炎（CMV-1P）；多为既往CMV感染被激活，对CMV—DNA阳性而无症状者进行预防治疗可使CMV—DNA阴转，可降低CMV病的发生。结论CMV病是allo—HSCT的常见并发症及主要致死原因之一；因此积极防治GVHD的发生及发展、定期监测CMV血清学阳性患者、早期干预性治疗可以提高移植的成功率。     

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.     

Use of PCR and PCR-SSP for detection of urinary donor-origin DNA in renal transplant recipients with acute rejection

Objective To analyze the urine of renal recipients for the pressence of donor DNA in an attempt to establish an alternative diagnostic means of acute rejection.Methods Sixty-four renal transplant recipients were examined.Thirty-seven were normal after transplantation,while 22 others developed acute rejection,based on serum creatinine levels and/or needle biopsy findings of the graft.Five developed drug-induced renal dysfunction.In female recipients with a male graft,we examined urine for the presence of Ychromosome(SRY and DYZ-1) and in recipients receiving and HLA mismatched graft,we looked for HLA-DR gene(DRB1)using PCR.Results Among the 14 female recipients with male grafte demonstrating stable renal function,only one was positive for SRY and DYZ-1 on the Y chromosome.However,sry AND DYZ-1 were found in the urine of four female patients with acute rejection,but these DNA fragments were not detected in 3 of the 4 after anti-rejection therapy.The last patient was referred to hemodialysis.Of 23 recipients of a graft from HLA mismatch donors with stable renal function,DRB1 was negative in 21(91%).Of 18 patients with acute rejection,DRB1 was positive in 16(89%)and negative in 2.these ENA fragments were no longer found in 13 patients after anti-rejection therapy.In all patients with drug induced renal dysfunction,donor-derived DNA was negative.Conclusions Presence of door specific DNA in the urine of the recipient is strongly associated with acute rejection.Analysis of dna DNA derived from donor cells in urine was an effective and accurate method for the diagnosis of acute rejection of a renal transplant.     

异基因外周血造血干细胞移植并巨细胞病毒感染的分析

目的探讨异基因外周血造血干细胞移植(PBSCT)中对巨细胞病毒(CMV)感染的监测及早期干预性治疗的可行性。方法对2005年1月~2006年12月在上海交通大学附属第一人民医院接受异基因PBSCT的35例患者进行回顾分析,分析CMV病的发生率及其相关的危险因素。结果35例患者中22例发生CMV血症,6例出现CMV病。其中2例发生CMV间质性肺炎(CMV-IP),均治疗无效死亡。通过CMV-DNA检测,对结果阳性而无临床症状者进行干预性治疗使CMV-DNA转阴,同时减少可能导致CMV病发生的高危因素,则可降低CMV病发生率。结论CMV病是异基因PBSCT的常见并发症,也是主要致死原因之一。本组所采用的方法可减少CMV病的发生率及CMV病的病死率。     

Detection of cytomegalovirus by the polymerase chain reaction. A simple, rapid and sensitive non-radioactive method.

Cytomegalovirus (CMV) is an important pathogen in persons who are immunocompromised or who have received organ transplants. The rate of symptomatic CMV infection is relatively higher after liver transplantation, and CMV hepatitis may be difficult to differentiate from rejection or cholangitis without recourse to liver biopsy and tissue culture. In this study we have used the polymerase chain reaction (PCR) to amplify and detect CMV-DNA sequences directly from the saliva and urine of liver transplant recipients. The procedure is simple, rapid and specific, and was found to be as sensitive as tissue culture for the diagnosis of CMV.     

探讨肾移植术后肺部巨细胞病毒感染的诊断与治疗

目的探讨肾移植术后肺部巨细胞病毒(CMV)感染的临床特点及治疗对策。方法回顾总结本院18例肾移植术后肺部CMV感染临床资料。结果18例肾移植术后肺部CMV感染病人经更昔洛韦为主的综合治疗治愈16例,死亡2例。结论对肾移植术后肺部CMV感染应该尽早诊断,及时应用以更昔洛韦为主的综合治疗。     

MICA抗体监测在肾移植术后急、慢性排斥反应中的意义

目的探讨肾移植受者的抗MICA抗体水平与急性和慢性排斥反应的相关性及其对移植肾功能的影响。方法采用酶联
免疫吸附方法检测接受同种异体肾移植手术的患者血清中MICA 抗体,并同步检测HLA抗体、肾功血肌酐、尿量及移植肾超声
等临床指标。本研究分两部分分别监测在肾移植术后急、慢性排斥反应中MICA抗体的变化。结果第一部分41例研究对象
中有18例发生急性排斥反应,该组中MICA抗体阳性率高于肾功能稳定组（P<0.05）;MICA抗体阳性组的急性排斥反应发生率
高于MICA抗体阴性组（P<0.05）;术后MICA抗体动态监测时发现,MICA抗体水平逐渐升高2~3 d后出现排斥反应,给予抗排
斥治疗后血肌酐水平逐渐降至正常,MICA抗体水平亦逐渐下降,但仍维持在阳性范围。第二部分40例患者中21例患者出现
慢性排斥反应,其中MICA抗体阳性率明显高于肾功稳定组患者（P<0.05）。慢排组中MICA抗体阳性患者的血肌酐与阴性组
的血肌酐水平比较有统计学差异（P<0.05）。移植肾穿刺病理结果显示MICA抗体阳性患者C4d沉积均为阳性。结论MICA
抗体可预测急性排斥反应的发生及治疗效果,对于及时诊断及治疗排斥反应提供了一个重要指标,同时也是导致慢性排斥的主
要因素之一,可影响移植肾的长期存活。
     

Preoperative single-bolus high-dose antithymocyte globulin as induction therapy in sensitized renal transplant recipients

Background Immunological sensitization remains a major problem following renal transplantation. There is no consensus for the management of sensitized renal allograft recipients. The patients become tethered to dialysis while waiting for compatible donors. This study was designed to evaluate the efficacy and safety of preoperative single- bolus high-dose antithymocyte globulin (ATG) as induction therapy in sensitized renal transplant recipients.Methods A total of 56 patients were divided into two groups according to the level of panel reactive antibody (PRA): non-sensitized group (PRA&lt;10%, n=30) and sensitized group (PRA≥10%, n=26). The characteristics of the recipients and donors were comparable between the two groups. Mycophenolate mofetil (MMF, 1 g) or ATG (iv. 9 mg/kg) were given preoperatively in the two groups as induction therapy. After the transplantation, the patients were treated with standard triple therapy regimen consisting of tacrolimus (FK-506) or cyclosporine A, MMF, and prednisolone. Acute rejection (AR) and infection episodes were recorded and renal function was monitored during a 12-month follow-up. χ(2) test and t test were used to analyze the data.Results During the follow-up, 6 patients (20.0%) suffered AR episodes in the non-sensitized group and 4 (15.4%) in the sensitized group (P=0.737); 8 patients (26.7%) experienced 11 infection episodes (average, 1.4 episodes per infected patient) in the non-sensitized group, and 6 (23.1%) experienced 10 infection episodes (average, 1.7 episodes per infected patient) in the sensitized group (P=0.757, 0.890). The safety of the drugs, which was assessed by the occurrence of side effects, was comparable between the two groups. The hospital stay was 13－25 days (mean, 16.7±3.3) in the non-sensitized group and 14－29 days (mean, 16.2±3.1) in the sensitized group, respectively (P=0.563). No delayed graft function (DGF) was observed in all the patients. Both the 12-month actuarial patient and graft survival rates were 100% in the two groups.Conclusion Preoperative single-bolus high-dose ATG is an effective and safe induction therapy yielding acceptable acute rejection rate in sensitized renal transplant recipients.