Transfer of latent atopy by bone marrow transplantation? A case report

A previously healthy 8-year old girl was diagnosed with acute myelogenous leukemia, and, while she was in first remission, she received a bone marrow transplant from her atopic brother. Studies 1 to 2 years after transplantation revealed that the marrow recipient had a specific-IgE production of donor-type pattern, indicated by the similar skin prick test results and RAST scores in the donor and recipient demonstrating allergy to animal dander and house dust. The recipient's own immunity had been destroyed by the preparative regimen for marrow transplantation, and no lymphoid cells of host origin could be found after transplantation in the chromosome analysis. A sensitization of the recipient to animal dander after transplantation was very unlikely because no animal contacts were present, and the chronic liver graft-versus-host disease of the patient additionally suggested a delayed immunologic recovery. The case history suggests that atopy can be transferred by bone marrow transplantation from donor to recipient. A possible mechanism appears to be a passive transfer not only of lymphoid precursors but also of mature memory cells within the bone marrow inoculum. The donor memory B cells are presumably capable of starting specific-IgE production when the cells are stimulated in the host environment by factors still unknown.     

Auxiliary partial liver transplantation for end-stage chronic liver disease

Auxiliary heterotopic liver transplantation is theoretically attractive because it leaves the recipient's liver in place. The surgical trauma of hepatectomy is avoided, and failure of the graft does not necessarily lead to the death of the patient or a second, emergency transplantation. Another advantage is that matching the body sizes of the donor and the recipient is not mandatory, which increases the number of possible donors. However, previous clinical results of auxiliary liver transplantation have been poor. We performed auxiliary partial liver transplantation in six consecutive patients with end-stage chronic liver disease who were not accepted for orthotopic liver transplantation because they had massive ascites, deficient clotting function, cachexia, or poor pulmonary reserve. The donor liver was transplanted to the right subhepatic region after removal of segments II and III, and it was provided with portal and arterial blood. There were no major changes in hemodynamic measurements during surgery. The mean hospital stay after transplantation was 22.7 days (range, 14 to 29). After a mean follow-up period of 14 months (range, 5 to 23), all patients were alive, with good graft function as demonstrated by scintigraphy, Doppler ultrasonography, and synthesis of clotting factors. From these observations we conclude that auxiliary partial liver transplantation is an attractive alternative to orthotopic liver transplantation in high-risk patients. Its role in other patients who need liver transplants remains to be defined.     

供肝NK细胞对肝移植免疫反应中NF-κB 活性和IL-15表达的影响

 目的：观察大鼠移植肝组织内和外周血白细胞介素15（IL-15）的表达水平及脾组织内核因子κB(NF-κB)的表达活性变化,探讨供肝NK细胞减轻肝移植术后急性排斥反应的机制。方法：Lewis大鼠为肝移植供体,BN大鼠为受体,改良“二袖套”法建立大鼠肝移植模型。应用［60Co］射线照射清除供体免疫细胞和经门静脉回输供肝NK细胞等技术,实验设立3组。A组: 急性排斥组;B组: 单纯［60Co］照射排斥组;C组: ［60Co］照射+供肝NK细胞门静脉回输排斥组。移植术后第1、3、7天收集受鼠外周血清,ELISA法检测IL-15分泌水平,同时切取移植肝行病理学检查,Western blotting法检测移植肝组织IL-15蛋白的表达,凝胶电泳迁移实验（EMSA）检测受鼠脾组织NF-κB表达活性。另外每组各设亚组观察移植后大鼠自然生存时间。结果：B组术后大鼠自然存活时间较A、C组明显缩短,术后发生急性排斥反应程度较A、C组严重;术后第3、7天,3组受鼠外周血IL-15水平均较第1天时显著升高;移植术后第3、7天,B组大鼠血清IL-15 浓度均显著高于A、C组;术后第3、7天,移植肝组织中B组IL-15表达也显著高于A、C组,受鼠脾组织中B组NF-κB表达活性亦显著高于A、C组。结论：IL-15可能作为肝移植急性排斥反应的监测指标,对急性排斥反应的早期诊断和移植物的预后估计具有临床指导意义;供肝NK细胞可能通过下调NF-κB的表达活性来调节IL-15的水平,进而减轻肝移植术后急性排斥反应。     

Examination of serum class I antigen in liver-transplanted rats

We examined the appearance of donor (DA) type class I antigen in the serum of rats that had received isogeneic (DA----DA) or allogeneic (DA----PVG, DA----BN, DA----LEW) liver transplants with or without cyclosporin A treatment, using two-site enzyme immunoassay. We also tested the serum titre of class I antigen in the normal DA rats with either 70% hepatectomy or cyclosporin A treatment, in order to clarify the relationship between the fluctuation in the serum titre of class I antigen in the recipient and the outcome of the transplanted liver graft. The suppression of liver graft rejection by cyclosporin A treatment significantly lowered the serum level of donor liver-derived class I antigen as compared with that of the recipient without cyclosporin A for a certain period. However, there was almost no correlation between the intensity of rejection of the liver graft and the serum level type class I among these allogeneic rejection and non-rejection liver transplantation combinations. The amount of donor-type class I antigen in the recipient's serum is dependent on whether the grafted liver is severely damaged following partial hepatectomy, whether the liver has associated biliary complications or ischaemic damage, or whether the liver has had absolute residual parenchymal cell volume or function following liver rejection. Our results suggest that the appearance of donor type class I antigen following liver transplantation is dependent on many factors, and therefore the titre of serum class 1 antigen may not always be a decisive indicator of liver graft rejection.     

活体肝移植和尸体肝移植过程中患者肾功能的比较

背景：原位肝移植中诸多因素可导致移植后急性肾功能衰竭,但不同移植方式对移植过程中患者肾功能的影响并不清楚。 目的：比较活体部分供肝移植和尸体全肝移植对移植过程中患者肾功能的影响。 方法：纳入拟行活体部分供肝原位肝移植的晚期肝病患者15例设为活体组,采用背驮式原位肝移植;另与同期进行的尸体全肝移植20例患者设为尸体组,采用非转流经典原位肝移植。分别于切皮前即刻、切皮后1 h、无肝期30 min、新肝期1 h及新肝期4 h测定血流动力学和肾功能指标。 结果与结论：两组患者各时间点平均动脉压、心率比较差异无显著性意义(P > 0.05),活体组无肝期30 min时心输出量、心指数高于尸体组,而体循环血管阻力、体循环血管阻力指数低于尸体组(P < 0.05)。两组移植过程中各时点血清胱抑素C、β2-微球蛋白、肌酐及肌酐清除率均在正常范围内,总尿量及呋噻米用量比较差异无显著性意义(P > 0.05),但活体组无肝期分钟尿量明显多于尸体组(P  < 0.05)。提示活体部分供肝移植和尸体全肝移植对移植过程中患者肾功能均未产生不利影响。     

预输注RelB shRNA慢病毒修饰树突细胞诱导大鼠肝移植免疫耐受

背景：肝移植后的排斥反应是威胁患者和移植物长期存活的主要原因。诱导受者产生特异性免疫耐受是解决排斥反应的理想措施。 目的：探讨RNAi RelB树突状细胞预输注诱导大鼠肝移植特异性免疫耐受的可能性。 方法：将近交系雄性清洁级DA(RT1a)大鼠和近交系雄性SPF级Lewis(RT11)大鼠分别作为供、受体,行原位肝移植手术。术前随机配对分为4组：①对照组,受体鼠移植前不做预输注。②治疗组：受体鼠移植前7 d静脉输注供体大鼠RNAi RelB树突状细胞(5×106)。③未成熟树突状细胞组：受体鼠移植前7 d静脉输注供体大鼠未成熟树突状细胞(5×106)。④成熟树突状细胞组：受体鼠移植前7 d静脉输注供体大鼠成熟树突状细胞(5×106)。 结果与结论：与对照组、未成熟树突状细胞组以及成熟树突状细胞组相比,治疗组移植肝的平均生存时间显著延长。移植后第7天,治疗组天冬氨酸转氨酶,总胆红素水平低于对照组、成熟树突状细胞组、未成熟树突状细胞组(P < 0.01),移植后第14天治疗组、未成熟树突状细胞组天冬氨酸转氨酶,总胆红素均有轻微下降,两组比较差异仍有显著性意义(P < 0.01)。移植后第7天,与治疗组比较,对照组、成熟树突状细胞组、未成熟树突状细胞组γ-干扰素、白细胞介素2水平升高(P < 0.01),而白细胞介素4、白细胞介素10下降(P < 0.01);移植后第14天治疗组、未成熟树突状细胞组γ-干扰素、白细胞介素2水平均有下降,白细胞介素4、白细胞介素10水平均有升高,两组比较差异仍有显著性意义(P < 0.01)。对照组、成熟树突状细胞组、未成熟树突状细胞组移植后第7天排斥活动指数为8.0-9.0。未成熟树突状细胞组第14天肝细胞、内皮细胞坏死及汇管区炎性细胞浸润进一步增多。治疗组移植后第7天排斥活动指数为6.0-8.0,第14天时排斥活动指数为4.0-5.0。结果提示RNAi RelB树突状细胞预输注可以减轻移植肝排斥程度,延长移植肝生存时间,这是通过间接途径实现的,其机制可能与T细胞的调节和无能有关。     

Immunologic and plasma protein studies in a splenic homograft recipient

A report is given of the immunologic and haematologic changes in a 24-year-old man with juvenile Gaucher's disease who received a splenic homograft from an unrelated living donor. To judge from the spleen scans, the graft functioned for 6 weeks. During the latter part of this time erythrocytes with donor markers were detected in the recipient's blood, and at the same time antibodies to one of the donor erythrocyte antigens appeared. No lymphocytes of donors type or cytotoxic antibodies to such lymphocytes were found. Three weeks after the transplantation the immunologic reactivity of the recipient lymphocytes, as measured in vitro, was decreased. There were no significant changes in the plasma level of immunoglobulins or coagulation factors.     

Assessment of donor liver steatosis: pathologist or automated software?

Steatosis in donor liver biopsy specimens has been shown to correlate with graft dysfunction after orthotopic liver transplantation. This 2-part (laboratory pilot, clinical retrospective) study compared the traditional interpretation of steatosis by a pathologist with an automated measurement determined by an image analysis system. In our pilot study, Sprague-Dawley rats were studied prospectively by feeding them a choline-deficient diet for up to 7 days. In our clinical group, data from 49 consecutive recipients of cadaveric liver transplantation were reviewed retrospectively. In both studies, the percentages of microvesicular fat, macrovesicular fat, and total fat content within liver biopsy specimens were determined by an automated image analysis software program and a pathologist using the same set of slides. The association between fat content of the donor liver and patient survival and graft survival, along with levels of aspartate aminotransferase, alanine aminotransferase, prothrombin time, and total bilirubin after transplantation, were also examined in the clinical study. A direct correlation was observed between levels of macrovesicular fat determined by a pathologist and the automated software using livers from rats fed a choline-deficient diet and livers from deceased donors. A significant association was observed between macrovesicular fat content in the donor liver biopsy and graft survival by both techniques. We conclude that an image analysis system can be used to automate the determination of fat content in liver biopsy specimens, and that its findings correlate with both the visual interpretation by a pathologist and graft survival. Further study is needed to determine the role of an automated technique in the evaluation of donor livers for transplantation.     

Direct evidence for GB virus C/hepatitis G virus (GBV-C/HGV) superinfection: elimination of resident viral strain by donor strain in a patient undergoing liver transplantation

The viral genome of GB virus C/hepatitis G virus (GBV-C/HGV), a single-strand RNA virus, is subject to considerable variability and at least four genotypes have been suggested based on phylogenetic analysis. While co-infection of GBV-C/HGV with other infectious agents such as hepatitis C virus (HCV) has been frequently observed, there is no report whether or not co-infection and/or superinfection occurs among different GBV-C/HGV strains. By studying a GBV-C/HGV positive recipient/donor pair in the context of undergoing liver transplantation, we have sequenced multiple clones derived from serum samples serially collected over four years. Detailed phylogenetic analyses have been performed with these sequences. The donor was infected with GBV-C/HGV genotype 1 and this strain completely replaced recipient GBV-C/HGV strain (genotype 2) after liver transplantation. The recipient's original viral strain became undetectable during follow-up. Sequence analysis failed to identify genetic recombination between the two genotypes, at least in whole structural domain. This study, therefore, provides direct evidence for GBV-C/HGV superinfection of one strain by another with one of them predominating probably due to replication competition.     

Computer micromorphometry of allotransplanted human kidneys

Quantitative changes of structural correlations of transplanted allogenic human kidneys were examined in the histological slides by means of computer micromorphometry. The measurements were performed in 663 transplants selected randomly which had been in the recipient's body from several hours till 14.5 years. As a result of the study, parameters of glomeruli, tubules, blood vessels and connective tissue in the overall mass of donor kidneys were established starting from the time before transplantation and 6 months, 1-1.5, 2-3, 4-5, 7-14.5 years after transplantation. A progressive increase of sclerotic changes in the transplant is confirmed and the hypotheses about their genesis are proposed.     

Absence of hemolysis after a kidney transplant in an E+ recipient from a donor with anti-E

A 12-year-old Caucasian male with cystinosis received a kidney from his mother, whose red blood cells typed as group O, D+, E-. Her serum contained an anti-E with an IgG1 titer of 16 (score 31). The recipient's type was group O, D+, E+, with a negative antibody screen in the pretransplant period. The recipient and donor Rh phenotypes were most likely DCcEe and Dccee, respectively. Because the recipient's mother had no transfusion history, she was probably immunized by the fetal red blood cells of her one pregnancy (the recipient). The kidney had been immediately perfused with saline after removal from the donor. No acute or delayed hemolysis was observed clinically or in laboratory tests performed immediately after the transplant and at 7, 15, and 30 days after the transplant. Antibody screens were still negative at 6 months. In this case, anti-E was not present in the transplanted kidney in sufficient concentration to cause hemolysis of the recipient's red blood cells and transplanted lymphocytes did not synthesize sufficient anti-E to be detectable or to cause hemolysis.     

脂肪肝供肝对肝移植术后早期肝功能的影响

目的 探讨脂肪肝供肝对肝移植术后早期肝功能的影响,评估脂肪肝供肝肝移植术的临床疗效和安全性。方法 回顾性分析2007年1月—2012年3月在南京军区福州总医院行经典原位肝移植的26例肝细胞肝癌患者的临床资料。根据供肝（均为尸肝）病理检查结果,按其脂肪变性程度将26例患者分成3组：无脂肪变性组（正常组）10例,轻度脂肪变性组（轻度组）10例,中度脂肪变性组（中度组）6例。观察比较各组分别于术后第1、3、5、7、14天肝功能指标恢复情况。结果 3组患者手术均顺利完成,术中无意外情况发生,术后各组无一例移植物原发性无功能。与正常组相比,轻度组术后第1、3、5、7、14天的ALT、AST、凝血酶原时间（PT）、总胆红素（TBIL）差异均无统计学意义（P值均〉0．05）;中度组术后第1、3、5天ALT、AST、PT均明显高于正常组和轻度组（P值均〈0．05）,而TBIL术后第1、3、5、7、14天与正常组及轻度组相比,差异均无统计学意义（P值均〉0．05）。26例患者术后随访20～75个月,平均（38．6±18．2）个月。正常组、轻度组及中度组术后1年生存例数分别为8例、9例、5例,差异均无统计学意义（He=0．379,P=0．828）。结论 轻度脂肪肝供肝对术后早期肝功能无明显不利影响,可安全应用于临床肝移植;中度脂肪肝供肝肝移植术后早期肝功能恢复较无脂肪变性者和轻度脂肪变性者慢,临床上可以用于一般状况较好的患者。     

Alternative approaches for the induction of transplantation tolerance

The immunosuppressive drugs currently in use in clinical transplantation are undoubtedly very effective at controlling graft rejection. However, their use is associated with a large number of side-effects, both immunological and non-immunological, particularly in the longer term. From an immunological point of view, the major disadvantage of these agents is that their mode of action is immunologically non-specific, resulting in blanket or pan-immunosuppression of the recipient's immune system. Thus, not only is the recipient's immune response against the organ graft suppressed, but responses to all other antigenic stimuli such as viral infections are also prevented. The transplant recipient can therefore become severely immunocompromised as a result of the drug therapy and is susceptible to opportunistic infections and an increased incidence of cancer. One of the aims for the design of new immunosuppressive therapy is to develop protocols that are both effective and immunologically specific, such that only the immune response to the transplanted organ is suppressed. The optimal approach would be to induce tolerance to the donor histocompatibility antigens before transplantation, permanently paralysing the ability of the recipient's immune system to mount a rejection response against the graft. Some of the approaches for the induction of immunological tolerance currently being explored in clinical transplantation will be discussed. These include total lymphoid irradiation (TLI) and donor bone marrow transfusion combined with anti-lymphocyte globulin (ALG) post-transplantation. In addition some new approaches for the induction of tolerance before transplantation currently being investigated in experimental systems will be presented.     

Transferral of malignancy as a complication of organ transplantation: an insuperable problem?

A case of inadvertent transplantation of malignancy is presented in detail. The donor was a 36-year-old woman with an unsuspected disseminated carcinoma of lung, and the renal and tumour transplant recipient a 53-year-old man. The transplanted tumour remained clinically "silent" and was discovered only a necropsy after the recipient's death from ischaemic heart disease. The phenomena of de novo primary and transferred (donor) malignancy in organ recipients, along with related immunological considerations, are briefly reviewed. Finally, with regard to the increasing frequency and variability of organ transplants, the routine clinical practice required to minimise the risk of these complications is re-emphasised, with additional recommendations.     

丹参对大鼠移植肝血红素氧合酶1表达的影响

背景：器官移植前使用丹参预处理能够保护组织缺血-再灌注损伤,改善移植器官存活率。 目的：观察含丹参的冷灌注液对同种异体大鼠移植肝脏中血红素氧合酶1表达的影响,以及对供体肝脏缺血-再灌注损伤的保护作用。 方法：将SD雄性大鼠随机分成UW液组(术中使用UW液灌注保存)、丹参+UW液组(术中使用丹参+UW液灌注保存)、ZnPP预处理组(移植前24 h腹腔内注射ZnPP,术中使用丹参+UW液灌注保存),建立稳定的大鼠同种异体肝移植模型。同时取10只正常大鼠作为正常对照。 结果与结论：丹参+UW液组和UW液组血清总胆红素、谷丙转氨酶、谷草转氨酶水平明显低于ZnPP预处理组(P < 0.01)。血红素氧合酶1mRNA及其蛋白在丹参+UW液组中较UW组表达更明显,在ZnPP预处理组中表达明显受到抑制(P< 0.05)。丹参+UW液组肝脏Suzuki标准评分明显低于ZnPP预处理组及UW液组(P < 0.05)。表明丹参能上调同种异体的大鼠移植肝脏中血红素氧合酶1 mRNA及其蛋白的表达,减轻供肝缺血-再灌注损伤,保护移植大鼠肝脏。     

Histopathology of serial graft biopsies from liver transplant recipients

Serial graft biopsies (n = 78) from 12 liver transplant recipients (followed clinically up to 47 months) were studied with the use of histology, histochemistry, immunostaining, and electron microscopy. Planned-protocol needle biopsy specimens were taken from the graft before removal from the donor, 1 hour after transplantation, on the eighth day, and at yearly intervals. Nonprotocol biopsies were taken when deterioration of the clinical condition made a decision on changes in the regimen necessary. The protocol biopsies provided a baseline for graft condition and diagnostic histopathologic features. In these biopsies signs of hyperacute rejection, chronic rejection, or the recipient's previous liver disease were not observed. Mild acute rejection was regularly present on the eighth day, possibly due to a lag phase in the effect of immunosuppression. The syndromes in the nonprotocol biopsies included "pure" parenchymal cholestasis, reversible acute rejection resembling chronic active hepatitis, viral infection, and acute bacterial cholangitis. Each of these syndromes correlated with a separate histopathologic entity. Therefore, these entities proved to be of diagnostic value. It is concluded that a graft biopsy may substantially add to the pathogenetic interpretation, differential diagnosis, and management of major graft syndromes in orthotopic liver transplant recipients.     

非HLA因素致大鼠肾移植CAN加快模型的建立

目的建立大鼠异体肾移植慢性移植肾肾病(CAN)加快模型,为研究非HLA免疫因素及非免疫因素致CAN的病因、病理及病理生理机制提供平台。方法采用雄性Fisher大鼠和Lewis大鼠分别作为供-受体,并以假手术组作为对照,进行异体原位肾移植。受体移植术前对供肾进行强化冷缺血处理1 h,于术后4 w,8 w,12 w分别观察各受体血肌酐和移植肾组织病理变化情况。结果移植术后4周Fisher-Lewis组开始出现血肌酐的升高及移植肾CAN的病理改变,8~12周病变渐趋明显,与对照组比较有统计学差异(P<0.05)。结论以Fisher和Lewis近交系大鼠作为供-受体建立的大鼠异体肾移植CAN加快模型是一种可靠、实用和研究价值高的肾移植实验动物模型。     

亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的应用

背景：亲属活体肾移植供、受者移植前准备充分,供肾热、冷缺血时间较短,HLA配型的组织相容性好,移植后排斥反应发生率低,为亲属活体供肾肾移植后采用低剂量免疫抑制剂方案提供了可能性。 目的：探讨亲属活体供肾移植后低剂量钙调蛋白酶抑制剂的安全性和有效性。 方法：选取2006-01/2008-06在南京医科大学第一附属医院肾移植中心行亲属活体供肾移植的受者38例,移植后常规使用环孢素A/他克莫司+吗替麦考酚酯+泼尼松的三联免疫抑制方案。将38例患者随机分为两组：CNI常规剂量组(n=18),移植后初始药物剂量为环孢素A 6 mg/(kg•d)或他克莫司0.12 mg/(kg•d);CNI低剂量组(n=20),术后初始药物剂量为环孢素A 4 mg/(kg•d)或他克莫司0.08 mg/(kg•d);两组吗替麦考酚酯和泼尼松使用剂量相同。移植后密切随访,比较两组患者移植后不同时期的肾功能以及急性排斥反应、肺部感染、肝功能损害、肾毒性等并发症的发生情况。 结果与结论：随访12个月,CNI常规剂量组重度肺部感染死亡1例,CNI低剂量组无死亡病例。两组移植肾功能及急性排斥反应发生率比较差异均无显著性意义(P > 0.05);CNI低剂量组肝功能损害、钙调蛋白酶抑制剂肾毒性发生率显著低于CNI常规剂量组 (P < 0.05)。此外,采用低剂量钙调蛋白酶抑制剂免疫抑制方案明显减轻了亲属肾移植患者的经济负担。说明亲属活体供肾移植后采用低剂量钙调蛋白酶抑制剂的免疫抑制剂方案安全、有效。     

Effect of thymus grafts of various ages on the immune system formation in CBA mice

An attempt has been made to govern the development of immunological capability in CBA mice by means of transplantation at an early postnatal period of thymus from donors of various ages. The results have shown that in thymectomized animals, apart from a well known gradual decline with the donor's age in restorative functions of the transplanted thymus, there was at the age of 22 months a phase of inhibitory influence on the recipient's immune system. In intact animals, transplantation of the thymus from a 5-day-old donor caused a decrease and that from a 22-month-old donor caused an increase in the development of the capacity for immune response. Taken together, our findings indicate an active role of the thymus both in the formation of the immune system and in its alteration with aging.     

Detection of T suppressor cells in patients with organ allografts

Specific immunosuppression of host's immune response to donor HLA antigens has been a major goal to clinical transplantation. Recent evidence has been accumulating to show that a distinct population of T cells expressing the CD8(+) CD28(-) phenotype display suppressor function and inhibit Th activation and proliferation by modulating the APC function. To assess the presence of Ts in transplant recipient's circulation, we have developed a flow cytometry method that measures the expression of costimulatory molecules on donor APC exposed to recipient Th and Ts. Our results demonstrate that quantitation of the capacity of CD8(+) CD28(-) T cells from patient circulation to suppress the activation of costimulatory molecules (CD80, CD86) on donor APC offers a reliable tool for monitoring specific immunosuppression against the graft in solid organ transplantation.