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。     

雷公藤多甙对大鼠原位肝移植急性排斥反应的影响

目的 探讨雷公藤多甙(TⅡ)对大鼠肝移植术后急性排斥反应的抑制作用和机制。方法 用“二袖套法”建立Wistar→SD大鼠原位肝移植模型，分对照组(n＝12)和TⅡ治疗组(n＝13)，移植术后第7d两组各杀死部分大鼠，测肝功能、肝组织病理和脾淋巴细胞IL—2活性，其余大鼠留作观察存活时间。结果术后第7d，TⅡ组肝功能损害和移植肝病理急性排斥反应程度轻于对照组，IL—2活性低于对照组。TⅡ组大鼠术后存活时间比对照组明显延长。结论 TⅡ可明显延长肝移植术后存活时间，减轻急性排斥反应程度。     

应用抗CD3单克隆抗体预防肾移植术后急性排斥反应的体会

目的 观察国产抗CD3单克隆抗体在预防肾移植术后急性排斥反应中的作用。方法 将60例患者随机分为3组，每组20例，3个组移植术后均给以环孢素A、硫唑嘌呤和皮质激素组成的三联免疫抑制方案；全量组加用抗CD3单克隆抗体5mg/d，半量组加用抗CD3单克隆抗体2.5mg/d，对照组不用。观察术后肾功能的恢复情况及急性排斥反应发生率。结果 术后1周使用抗CD3单克隆抗体者的血肌酐低于对照组（P＜0．05），10d后二者的差异无显著性；在术后头3个月，使用抗CD3单克隆抗体治疗组与对照组在急性排斥反应发生率方面的差异有显著性（P＜0．05）；使用抗CD单克隆抗体全量组与半量组在术后肾功能恢复及急性排斥反应发生率方面的差异无显著性。结论 术后早期预防性使用抗CD3单克隆抗体对移植肾功能的恢复和降低急性排斥反应发生率有较好的作用；给予半量的抗CD3单克隆抗体能取得与全量同样的效果，且费用较低，并发症少。     

高度致敏受者肾移植的临床处理

目的 总结高度致敏受者肾移植的临床处理经验.方法 26例群体反应性抗体(PRA)峰值≥50%的高致敏患者行同种异体肾移植术.男8例,女18例.平均年龄(47.6±7.4)岁.首次接受移植者15例,二次移植者10例,三次移植者1例.亲属供肾1例,尸体供肾25例.术前要求交叉配型阴性.术后采用抗CDzs单克隆抗体诱导,他克莫司加吗替麦考酚酯加激素三联维持治疗.结果 18例移植后1周内血肌酐(SCr)降至正常.2例分别于术后第2、3天出现加速性排斥反应,经过血浆置换3次及抗CD3单克隆抗体5 mg/d治疗5 d后,1例3周后移植肾功能逐渐恢复正常,另1例排斥反应未能逆转,最终摘除移植肾.发生急性排斥反应6例,2例经激素冲击治疗后逆转,4例为耐激素排斥反应,经抗CD3单克隆抗体5 mg/d治疗5 d和血浆置换治疗3次后,排斥反应逆转.1年移植肾存活率96%(25/26).结论 高度致敏受者肾移植不仅需要HLA配型良好,并且要求供者HLA抗原避开受者所有预存的抗HLA抗体;术后采用抗CD25单克隆抗体诱导,他克莫司加吗替麦考酚酯加激素三联维持治疗,能有效预防和治疗急性排斥反应.     

肝肾联合移植 22 例报告

目的 对临床肝肾联合移植(CLKT)进行总结. 方法 为22例肝功能衰竭合并尿毒症患者实施CLKT,每例受者所移植的肝脏和肾脏来自同一供者,采取原位灌注、多器官联合快速切取.10例行经典式原位肝移植术,12例行背驮式肝移植术,均未行静脉转流,肾移植采用常规术式,均为一期移植.术后采用抗胸腺细胞球蛋白或(和)抗CD25单克隆抗体诱导治疗,采用他克莫司、吗替麦考酚酯和泼尼松预防排斥反应. 结果 22例手术全部成功,移植肝和移植肾功能恢复良好.术后发生移植肝急性排斥反应1例,移植肾急性排斥反应2例,他克莫司中毒1例,上消化道出血1例,腹腔继发性出血1例.胸腔积液6例,肺部感染2例,腹腔感染1例.本组随访6个月至7年11个月,死亡3例,其中2例患者分别在术后第7个月和第10个月死于肺部巨细胞病毒感染,1例患者在术后第9个月死于急性心肌梗死.受者术后1、3、5年存活率分别为86.4%、81.3%和72.7%. 结论 CLKT是治疗终末期肝病合并肾功能衰竭的有效方法.     

全血中TNF-α、IL-6基因多态性对同种肝移植急性排斥反应的影响

目的寻找一种在肝移植术前可以预测急性排斥反应发生及其产生程度的方法。方法术前从全血中提取DNA,经过聚合酶链反应技术(PCR-SSP方法)扩增并检测肿瘤坏死因子鄄α(TNF鄄α)和白介素鄄6(IL鄄6)基因,建立猪的原位肝移植模型,术后根据病理变化,对同种异体肝移植术后急性排斥反应作出诊断。结果在46只动物中,29只发生急性排斥反应,具有TNF鄄α鄄308A/A及IL鄄6鄄124G/G的基因类型个体在排斥组与非排斥组中有显著性差别。结论具有TNF鄄α鄄308A/A及IL鄄6鄄124G/G的基因类型在肝移植后更易发生急性排斥反应。     

胆汁白细胞介素6和干扰素γ基因表达在大鼠肝移植急性排斥反应诊断中的意义

目的　探讨肝移植术后急性排斥反应的早期诊断方法。方法　应用RT PCR技术检测大鼠肝移植术后胆汁中的IL 6和IFN γ基因表达 ,以组织病理学作为急性排斥反应的诊断标准 ,将肝移植大鼠分为急性排斥组 (Rt组 )和非急性排斥组 (Rf组 ) ,观察胆汁中IL 6和IFN γ基因表达与急性排斥反应的关系。结果　胆汁中IL 6基因表达在Rt组和Rf组无显著性差异 (P >0 0 5 ) ,而IFN γ基因表达在Rt组和Rf组有显著性差异 (P <0 0 1)。结论　检测胆汁中IFN γ基因表达可能是早期诊断肝移植术后急性排斥反应的一个有效指标 ,而IL 6基因表达则无助于急性排斥反应的诊断。     

抗IL—2R单克隆抗体在肾脏移植中的应用

IL－2和IL－2R相互作用在T细胞活化，增殖中起关键作用，IL－2Rα单克隆抗体可以对被同种异体移植物激活的T细胞克隆选择性地产生免疫抑制,人而达到预防急性排斥反应的目的，III期临床试验结果表明，IL－2Rα单抗daclizumab(Zenapax)和basiliximab(Simulect)可将同种异体移植肾急性排斥反应的发生率降低27－40％，并未见明显的毒副作用。     

程序性死亡受体蛋白1单克隆抗体治疗肝移植术后肝癌复发的研究进展

目的探索肝移植术后肝癌复发患者应用程序性死亡受体蛋白-1(PD-1)单克隆抗体(简称"单抗")治疗的可行性、安全性以及需要解决的问题。方法对国内外有关肝移植术后应用PD-1单抗治疗的病例报道进行分析和总结。结果搜集到了6例肝移植术后肝癌复发患者应用PD-1单抗治疗,其中有3例患者发生了移植肝急性排斥反应,有2例患者治疗效果不佳但并无移植肝发生排斥反应的证据,有1例患者达到转移灶完全缓解且治疗期间无副反应及排斥反应发生。结论现阶段对于肝移植术后肝癌复发患者应用PD-1单抗治疗的效果尚不确切,在使用该药过程中必须严密监测其肝功能状况,警惕可能发生的移植器官急性排斥反应。     

肝、肾联合移植12例报告

目的 对肝、肾联合移植的临床情况进行总结。方法 为12例肝、肾功能异常患者施行肝、肾联合移植，采用多器官联合切取术整块切取供者器官。8例行经典式肝移植，4例行背驮式肝移植，均未行体外静脉转流；肾移植为常规术式。术前进行抗CD25单克隆抗体和抗胸腺细胞球蛋白诱导治疗，术后应用他克莫司（FK506）、霉酚酸酯及泼尼松预防排斥反应。结果 12例手术均获成功，移植肝及肾功能恢复良好。术后的并发症有移植肝急性排斥反应、FK506中毒、消化道出血、腹腔出血、肺部感染、腹腔感染（各1例次），所有患者均未发生移植肾急性排斥反应。结论 肝、肾联合移植是治疗终末期肝病合并肾功能衰竭的理想选择。     

Anti‐IL‐2R blockers comparing with polyclonal antibodies: Higher risk of rejection without negative mid‐term outcomes after ABO‐incompatible kidney transplantation

There is no recommendation regarding the type of induction therapy to use in ABO‐incompatible (ABOi) kidney transplantation. The aim of this retrospective study was to compare the outcome of ABOi living donor kidney transplant (LDKT) recipients who received either polyclonal antibodies or anti‐interleukin‐2 receptor (IL‐2R) blockers as an induction agent. All ABOi HLA‐compatible patients that received a LDKT between 03/11 and 03/18 in three French transplantation center (Paris Saint‐Louis, Paris Necker, and Toulouse) were included in the study. Fifty‐eight patients were given polyclonal antibodies and 39 patients received anti‐IL‐2R blockers. We identified by a Cox proportional hazard model the use of polyclonal antibodies as a protective factor against acute rejection (HR = 0.4, 95%CI [0‐0.9], P < .05). However, pathological findings on protocol biopsies at 1 year were similar in both groups, as were patient and graft survivals, renal function, and complications. We conclude that the acute rejection rate was significantly higher in patients given anti‐IL‐2R blockers compared to polyclonal antibodies. However, in our series, there was no negative impact on mid‐term outcome.     

Isolated Hepatic Chronic Ductopenic Rejection Requiring Liver Retransplant in the Absence of Kidney Graft Rejection After Combined Liver-Kidney Transplant: A Case Report

The liver is considered the most immunotolerant organ among all solid-organ transplants. Liver transplant recipients have a lower incidence of rejection and better outcomes after episodes of rejection, with spontaneous operational tolerance developing in up to 20%. In multiorgan transplants, a protective effect of the liver allograft on simultaneously transplanted organs from the same donor has been demonstrated. We describe an unusual case of isolated liver allograft rejection in a patient with polycystic liver and kidney disease who received a combined liver-kidney transplant from the same donor. After initial discharge from the hospital, our patient had 2 episodes of biopsy-proven late acute cellular rejections, despite higher levels of immunosuppression required for her kidney allograft, which were addressed with pulsed steroid therapy. She had no evidence of ischemic cholangiopathy on imaging. Later, a subsequent liver biopsy demonstrated features consistent with chronic ductopenic rejection. She was eventually listed for liver retransplant and has recently received a second liver transplant while continuing to have no concerns with her kidney allograft function. Examination of the explanted liver confirmed graft loss from chronic ductopenic rejection. The exact reasons why our patient developed acute graft rejection progressing to chronic end-stage rejection of the liver allograft despite not developing graft rejection in the kidney allograft from the same donor remains elusive. Our experience demonstrates that graft tolerance in multiorgan transplant recipients can be organ specific and despite the belief of “immunologic privilege,” isolated liver allograft rejection can occur in multiorgan transplant, resulting in graft loss.     

Efficacy of Anti-IL-2 Receptor Antibodies Compared to no Induction and to Antilymphocyte Antibodies in Renal Transplantation

The relative efficacy of anti-IL-2 receptor antibodies (IL2R Abs) and antilymphocyte antibodies in preventing acute rejection and improving graft survival after renal transplantation is poorly defined. In particular, the benefits of these agents in specific subgroups, such as recipients with different degrees of HLA mismatch, are unknown. Using the SRTR database, we compared IL2R Abs to no induction and to antilymphocyte antibody induction in 48 948 first renal transplant recipients in the United States between 1998 and 2003 with respect to acute rejection and graft failure. IL2R Abs decreased acute rejection at 6 months (OR: 0.81(0.75-0.87)), and reduced graft failure (HR: 0.90(0.84-0.95)), compared to no induction over a follow-up of 1059 days. Compared to IL2R Abs, antilymphocyte Abs were associated with decreased acute rejection (OR: 0.90(0.83-0.99)) at 1 year, but were not associated with improved graft survival (OR: 1.08(1.00-1.18)) over a follow-up of 732 days. The benefit of IL2R Abs in reducing acute rejection increased significantly with greater HLA mismatch (p = 0.007). IL2R Abs remain an important option in the management of renal transplant patients, and may be particularly useful in specific patient subsets.     

Should moderate acute rejection of a cardiac transplant graft be treated?

Histologically proven, moderate acute rejection after orthotopic heart transplantation (OHT) is commonly treated with intravenous steroids. This regimen may result in severe metabolic and infectious side-effects. The purpose of this study was to assess and compare outcomes in treated (T) versus not treated (N-T) biopsy proven 3A rejection episodes in cardiac transplant recipients. METHODS: A retrospective analysis was conducted to identify all biopsy proven 3A rejection episodes that occurred over the time period 1995-2000 in patients (patients) >or= 6 months after OHT (n=48 episodes in 35 patients). Of the 48 episodes, 19 were N-T and 29 were T. Decision to treat 3A rejection was based on time after transplant, haemodynamic and/or clinical compromise and left ventricular (LV) dysfunction measured by 2D echo. Most N-T episodes received an increase in background immunotherapy. RESULTS: Time from transplant to index 3A episode in N-T patients was 4.2 versus 2.7 yr for the T patients (p=0.06). There were no differences seen between T and N-T groups for the first and second post-3A biopsy results or LV function post-3A. Presence of coronary disease or death were not different between groups. Of the 29 patients with T episodes, no differences in outcomes (death, first and second post-3A biopsy score, coronary disease, myocardial infarction, or LV function) were seen based on use of treatment with intravenous versus oral steroid. CONCLUSION: In patients more than 6 month after OHT, there were no differences in outcomes (ongoing rejection or LV function) between N-T episodes of 3A rejection and T episodes. In T patients the use of oral steroids was equally as effective for treatment of 3A episodes as intravenous steroids.     

Impact of mycophenolate mofetil on recurrent rejection in kidney transplant patients

PURPOSE: Mycophenolate mofetil (MMF) has emerged as a valuable adjunctive agent in renal transplantation. However, due to intolerable adverse effects associated with MMF use in our transplant population, we have used MMF selectively in patients at high risk for recurrent graft rejection, since these patients are known to be at risk for poor long-term graft outcomes. The purpose of this study was to assess the efficacy of MMF in preventing the recurrence of acute rejection following an initial rejection episode in kidney transplant patients in the first year following transplantation. METHODS: Forty-four kidney transplant recipients were given MMF prospectively following treatment of their initial rejection episode to prevent recurrent rejection. MMF 1-2 g/d was given. Doses were adjusted based on tolerance; MMF therapy was to be continued for at least 6 months. The control group consisted of 124 consecutive kidney transplant recipients who had received standard anti-rejection therapy without the addition of MMF. Maintenance immunosuppression consisted predominantly of cyclosporine, prednisone+/-azathioprine. Anti-rejection therapy for both groups consisted of either corticosteroids (methylprednisolone 500 mg i.v. for 3 d or oral prednisone 2 mg/kg/d with rapid taper over 3 wk), OKT3 5 mg/d for 10 d or ATG 15 mg/kg/d for 10 d. All rejection episodes were confirmed by biopsy. RESULTS: The majority of rejection episodes were characterized histologically as mild or moderate. Most patients (76%) received corticosteroids for treatment of their first rejection episode. There was a 68% reduction in the incidence of recurrent rejection episodes within the first year of transplant in patients receiving MMF; only 14% of recipients receiving MMF developed recurrent rejection compared to 44% of patients in the control group (p<0.05). Approximately 50% of patients developed MMF-associated adverse effects (leukopenia, GI toxicity). Only 52% of patients remained on MMF at 6 months. One-yr graft survival was 86% in the MMF group and 89% in the control group (p>0.05). One-year patient survival was 93 and 100%, respectively (p>0.05). CONCLUSIONS: The addition of MMF to maintenance therapy for patients experiencing acute renal allograft rejection may prevent recurrent rejection episodes in the subsequent follow-up year.     

Tacrolimus for steroiD-resistant liver rejection in children

Abstract Eighteen pediatric liver transplant recipients were converted from cyclosporine-based immunosuppression to tacrolimus for refractory rejection episodes affecting 21 grafts. Before conversion, steroid boluses were applied to all episodes followed by OKT3 monoclonal antibodies in 3 of them. Baseline biopsy showed cellular rejection in 18 patients and ductopenia in 3 cases. Thirteen episodes initiated within the first 2 postoperative weeks, and 8 occurred beyond the 21st day. A previous steroiD-responsive episode of rejection was noted in 4 patients. Tacrolimus was administered by the oral route to obtain trough blood levels in the range 6–15 ng/ml. Reversal of rejection was obtained in 15 patients (71.4%). Complete normalization of liver function tests was achieved in 10 out of 12 patients who were followed for more than 6 months. A refractory evolution affected 6 patients (28.5 %). Significant factors predictive for tacrolimus-resistant rejection were identified as ductopenia on baseline biopsy, previous episodes of acute rejection, late onset rejection (beyond 21st posttransplant (day), and a longer time of evolution of rejection prior to conversion.     

A comparison of daclizumab to ATGAM induction in simultaneous pancreas-kidney transplant recipients on triple maintenance immunosuppression

Daclizumab (DAC) is a molecularly engineered humanized IgGa monoclonal Ab directed against the alpha chain of the interleukin‐2 receptor (IL2R). Inhibiting the amplification of the immune response by blocking IL2R can reduce the frequency of acute rejection without the attendant risk of infection.
The purpose of this retrospective study was to compare DAC to anti‐thymocyte (ATGAM) induction in 24 simultaneous pancreas–kidney (SPK) transplants performed between September 1995 and September 1998. The primary endpoints were the incidence within 6 months post‐transplant of: 1) biopsy‐proven acute rejection; and 2) infection. The two groups (DAC, n=12; ATGAM, n=12) were matched on age, race, ESRD, number of HLA mismatches, PRA level, and cold ischemia time. DAC (1 mg/kg) was given on the day of transplant, then every other week (a total of five doses); ATGAM (15 mg/kg) was given on post‐transplant day 1, then daily for 7–10 d. Immunosuppressive therapy consisted of cyclosporine (Neoral®– 8–10 mg/kg/d) or Prograf® (0.16–0.2 mg/kg/d), mycophenolate mofetil (CellCept®– 2–3 g/d) and steroids.
Of the 12 DAC patients, 3 patients (25%) had biopsy‐proven acute rejection versus 8/12 (67%) of the ATGAM patients. The time to acute rejection was significantly different by group (DAC=110 d; ATGAM=26 d). There was a reduction in the number of patients receiving antilymphocyte drugs for moderate to severe rejection (DAC=2/12; ATGAM=4/12), with 2 of the 4 ATGAM patients experiencing more than two episodes of biopsy‐proven rejection. There was an increase in infection by group (DAC=4/12; ATGAM=7/12): total of three septic infections occurred in the ATGAM group opposed to none in the DAC group. Patient, pancreas, kidney 6‐month survival rates were 100% for both groups.
We conclude that DAC induction coupled with triple immunosuppressive therapy reduces the incidence of rejection in SPK transplant patients. The time to acute rejection was prolonged in the DAC group compared with the ATGAM group without the attendant risks of rejection.     

Flow cytometry crossmatching as a predictor of acute rejection in sensitized recipients of cadaveric renal transplants

Flow cytometry crossmatching (FCXM) was developed as a more sensitive assay than the standard complement-dependent cytotoxicity crossmatch (CDCXM) for the detection of anti-donor antibodies, that mediate hyperacute rejection and graft loss in the early post-transplant period in renal transplant recipients. The role of FCXM in predicting long-term clinical outcome in renal allograft recipients is unclear. This study examines the role of FCXM in predicting long-term clinical outcome in highly sensitized recipients of cadaveric renal transplants. All patients (n = 100) with peak panel reactive antibody (PRA) levels > 30%, who received cadaveric renal transplants between 1/1/'90 and 12/31/'95 at our institution, were divided into FCXM + and FCXM - groups. The incidence of acute rejection was determined for each group during the first yr after transplant. Graft survival rates at 1, 2, and 3 yr, and creatinine levels were also compared between groups. FCXM + patients experienced a higher incidence of acute rejection during the first yr after transplant (69 vs. 45%), and a higher percentage of FCXM + patients had more than one episode of acute rejection during the first yr after transplant (34 vs. 8%) when compared to FCXM - patients. There was no statistically significant difference in 1-, 2-, or 3-yr graft survival between FCXM + and FCXM - patients (76 vs. 83, 62 vs. 80, 62 vs. 72%, respectively). These results suggest that sensitized FCXM + cadaveric renal transplant recipients have a higher incidence of acute rejection episodes in the first yr after transplant. Given the association of multiple rejection episodes with poor long-term allograft survival, FCXM may be a useful predictor of long-term clinical outcome in this sub-group of renal transplant recipients.     

Rejection is reduced in thoracic organ recipients when transplanted in the first year of life.

BACKGROUND: Infant heart transplant recipients have been reported to have decreased rates of rejection when clinical criteria are used for diagnosis. This study compares the rates of acute episodes of rejection in heart and lung transplant recipients transplanted in the first year of life to those of older recipients utilizing pathologic criteria. METHODS: Records of 100 consecutive lung transplant recipients (cystic fibrosis patients excluded) and 107 consecutive heart transplant recipients were reviewed with respect to: time to first rejection; total number; single versus multiple; and early (<90 days) versus late (>180 days) biopsy-proven rejection episodes. Rejection was defined as ISHLT biopsy Grade 3A or A2 for heart and lung transplant recipients, respectively. Biopsy and immunosuppression protocols were similar between groups. RESULTS: Kaplan-Meier analysis for freedom from rejection showed infant heart recipients were more often rejection-free (p = 0.004) as were infant lung recipients (p = 0.0001). Multivariate analysis revealed age at transplant as the most significant factor in predicting time to first rejection (age <1 year: risk ratio 0.19 [0.068-0.54] for lung transplant recipients and risk ratio 0.46 [0.27-0.78] for heart transplant recipients). Early rejection episodes occurred with less frequency in both the infant heart (19 of 63 [30%] versus 24 of 44 [50%]; p = 0.016) and lung (3 of 26 [12%] versus 63 of 74 [85%]; p = 0.001) groups. Late episodes of rejection were also less frequent in infant heart (4 of 53 [8%] versus 10 of 36 [28%], p = 0.016) and lung (0 of 23 [0%] versus 29 of 65 [45%]; p = 0.001) recipients. Multiple (> or =2) rejection episodes occurred less in infant heart (4 of 63 [6%] versus 9 of 41 [22%]; p = 0.037) and lung recipients (0 of 26 [0%] versus 17 of 74 [23%]; p = 0.003). CONCLUSIONS: These results demonstrate that age of <1 at time of thoracic transplantation confers significant protection from early, late and multiple episodes of acute rejection, as well as significantly greater freedom from rejection and time to first rejection.