微嵌合体诱导移植免疫耐受的研究进展

目前器官移植已经成为终末期器官功能衰竭患者的有效治疗手段,但是排斥反应仍然是器官移植术后早期功能障碍的最常见原因.通过新型免疫抑制剂的使用,可以使急性排斥反应的发生率明显下降,但同时会引起患者许多不良反应,而且免疫抑制剂对于移植慢性排斥反应和移植物的长期存活率无明显改善.     

抗体诱导治疗在肝移植中的应用进展

应用生物蛋白制剂——抗体作为器官移植早期实施免疫抑制覆盖治疗的方法,可显著减少器官移植术后早期急性排斥反应的发生,且未显著增加移植后感染发生率,同时可延迟或减少CNI的应用,有利于保护肾功能、促进移植物功能恢复及受者长期存活。本文通过总结常见抗体免疫诱导剂的特点及作用机制,分析不同抗体诱导治疗应用于肝移植的临床获益与风险,为肝移植抗体诱导剂的合理使用提供参考。     

中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)

肝脏虽为“免疫特惠器官”,肝移植术后急性排斥反应发生率及严重程度明显低于其他器官移植,但术后排斥反应仍较为常见,规范的免疫抑制治疗是保证移植效果的关键。为进一步规范肝移植术后免疫抑制治疗及排斥反应诊疗,中华医学会器官移植学分会组织肝移植专家,总结国内外相关研究最新进展,并结合国际指南和临床实践,针对肝移植术后免疫抑制剂应用原则、常用方案及各类型排斥反应的诊断与治疗,制订《中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)》。     

中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)

肝脏虽为"免疫特惠器官",肝移植术后急性排斥反应发生率及严重程度明显低于其他器官移植,但术后排斥反应仍较为常见,规范的免疫抑制治疗是保证移植效果的关键。为进一步规范肝移植术后免疫抑制治疗及排斥反应诊疗,中华医学会器官移植学分会组织肝移植专家,总结国内外相关研究最新进展,并结合国际指南和临床实践,针对肝移植术后免疫抑制剂应用原则、常用方案及各类型排斥反应的诊断与治疗,制订《中国肝移植免疫抑制治疗与排斥反应诊疗规范(2019版)》。     

肝移植术后急性排斥的诊断经验

急性排斥又称急性细胞性排斥(ACR),是由T淋巴细胞介导的细胞免疫反应,是器官移植术后排斥反应中最常见的一种。肝脏被称为“免疫特惠器官”,与心肺胰肾等其它器官移植相比,肝移植术后的急性排斥反应相对较轻且易于控制,但是其发生率并不低,早期的文献报道肝移植术后1年内急性排斥的发生率高达70%以上[1]。近年来由于新型免疫抑制剂的开发和应用,以及移植医师经验的积累增加,急性排斥发生率有下降的趋势,但是在肝移植临床急性排斥仍是一个经常可以见到的并发症,且急性排斥如处理不及时、处理措施不当或处理力度不够会转变为难治性排斥(或称…     

肝联合其他器官移植术后近期免疫抑制策略的方案探讨

目的探讨肝联合其他器官移植术后近期的免疫抑制策略。方法我中心于2004年至2009年共实施肝联合其他器官移植22例,其中肝肾联合移植17例,肝胰十二指肠联合移植5例。存活时间大于3个月的患者共18例,比较此类患者与单一器官移植患者术后近期排斥反应发生率和免疫抑制策略的差别。结果肝联合其他器官移植的患者术后3个月内,移植肝排斥反应发生率为5．5％;移植肾的排斥反应发生率为5．9％;其他器官没有发生排斥反应,较我中心单一器官移植排斥反应发生率低。同时,肝联合其他器官移植患者免疫抑制剂初始剂量及术后近期所需浓度均较单一器官移植低。结论肝联合其他器官移植的患者,由于移植肝对其他移植器官的免疫保护作用,排斥反应发生率低,所需免疫抑制剂初始剂量及浓度均低于单一器官移植。但肝脏对其他移植器官的免疫保护作用机制尚需进一步研究。     

霉酚酸酯在肾移植中的应用

排斥反应是引起肾移植术后移植肾功能障碍的重要原因之一 ,对新型免疫抑制剂的研究是有效的预防和治疗排斥反应的重要方法。霉酚酸酯作为一种新型的高效低毒免疫抑制剂在器官移植和自身免疫性疾病中得以广泛应用     

新型免疫抑制剂FK506在器官移植中的应用进展

新型免疫抑制剂ＦＫ５０６具有免疫抑制作用强、用药剂量少、毒副作用小等特点，可用于防止器官移植排斥反应的发生，治疗急性及早期出现的慢性排斥反应。临床上已开始作为肝、肾、心、肺、小肠等器官移植术后首选的免疫抑制剂，并已取得令人满意的效果。     

大鼠颈总动脉移植模型的建立

随着新型免疫抑制剂的应用和个体化治疗方案的实施,器官移植术后急性排斥反应得到了有效控制[1],慢性排斥反应及由此导致的移植物慢性功能丧失已成为限制移植器官及受者长期存活的主要因素[2].     

中国心脏移植免疫抑制治疗及排斥反应诊疗规范(2019版)

心脏移植免疫抑制治疗包括诱导、维持和抗排斥反应治疗。如何合理应用免疫抑制剂，制定个体化免疫抑制方案，在保证疗效的同时减少不良反应，仍是这一领域的难题。排斥反应是心脏移植术后常见并发症之一，涉及细胞免疫和体液免疫，其治疗原则主要取决于组织学证实的排斥反应级别和心功能损害程度。为进一步规范心脏移植免疫抑制治疗及排斥反应诊断和治疗，中华医学会器官移植学分会组织心脏移植专家，总结相关国内外最新进展，结合国际指南和临床实践，从免疫诱导治疗、维持免疫抑制剂的临床应用、排斥反应的识别以及急性排斥反应的诊断和治疗等方面，制订中国心脏移植免疫抑制治疗及排斥反应诊疗规范(2019版)。     

Kombinierte Nieren-Pankreas-Transplantation

BACKGROUND: Differences in graft survival due to gender have been reported after transplantation of the kidney, liver, and heart. However, little is known about the role of donor and recipient gender in simultaneous pancreas-kidney transplantation. METHODS: Single-centre analysis was performed of first simultaneous pancreas-kidney transplantations performed between 1994 and 2005 at the Bochum Transplant Center in Germany (n=218). RESULTS: Recipients of female donor organs exhibited acute organ rejections earlier and more frequently (P<0.05). Male recipients of organs from male donors had a lower risk of acute rejection than recipients of female donor organs (P<0.05). In addition to female donor gender, higher donor age and early kidney dysfunction were risk factors for perioperative rejection (P<0.05). Long-term kidney and pancreas function was best in male-donor-to-female-recipient transplants over the time periods of 7 and 3 years, respectively (P<0.05). Risk factors of long-term organ failure were: the need of revision laparotomy, organ rejection, and early postoperative organ dysfunction (P<0.05). CONCLUSION: This is the first report of graft function after simultaneous pancreas-kidney transplantation looking specifically at gender differences with respect to donor and recipient. There was an increased risk of organ rejection of female donor organs.     

Non-invasive imaging for the diagnosis of acute rejection in transplantation: The next frontier

Acute rejection is a leading cause of organ transplant failure and the most common indication for re-transplantation. Clinically, suspicion of acute rejection is often dependent upon serum laboratory values which may only manifest after organ injury. The gold standard for diagnosis requires an invasive biopsy which can carry serious clinical risks including bleeding and graft loss as well as the possibility of sampling error. The use of noninvasive imaging modalities to monitor transplanted organs is of great clinical value, particularly as a tool for early detection of graft dysfunction or acute rejection. Herein, we provide an overview of the existing literature evaluating noninvasive imaging modalities of solid organ and cellular allografts after transplantation, including both preclinical and clinical studies.     

Humoral and cellular rejection after combined liver–kidney transplantation in low immunologic risk recipients

Combined liver–kidney transplantation is considered a low risk for immunologic complication. We report an unusual case of identical ABO liver–kidney recipient without preformed anti-human leukocyte antigen (HLA) antibodies, transplanted across a T- and B-cell-negative cross-match and complicated by early acute humoral and cellular rejection, first in the liver then in the kidney. While analyzing the immunologic complications in our cohort of 12 low-risk combined liver–kidney recipients, only one recipient experienced a rejection episode without detection of anti-HLA antibody over time. Although humoral or cellular rejection is rare after combined kidney-liver transplantation, our data suggest that even in low-risk recipients, the liver does not always systematically protect the kidney from acute rejection. Indeed, the detection of C4d in the liver should be carefully followed after combined liver–kidney transplantation.     

Levosimendan treatment after primary organ failure in heart transplantation: a direct way to recovery?

Heart transplantation is considered nowadays the gold standard in the therapy of chronic and terminal heart insufficiency. Primary organ failure after heart transplantation is a severe complication generally related to prolonged ischemia time, poor quality of the organ, or acute rejection. All these factors can potentially lead to multiorgan failure. Pharmacological and mechanical support for these patients is limited and often related to side effects. Ca sensitizers have been proposed to increase cardiac contractility without altering intracellular Ca levels, thus avoiding the side effects of Ca overload. We report two cases of heart transplanted patients suffering from acute graft failure in the early postoperative period who recovered after intravenous administration of levosimendan, a Ca sensitizer.     

群体反应性抗体在肾移植中的意义

目的 研究群体反应性抗体（ＰＲＡ０在肾移植中的意义。方法 对１７８例肾移植患者进行了术前、术后ＰＲＡ检测。结果 肾移植术前ＰＲＡ阳性患者有２３例,肾移植术后发生急性排斥反应的为２０例。术后ＰＲＡ阳性受者５８例,发生排斥反应的有３４例。移植前后ＰＲＡ阴性患者有１０８例,有８例发生排斥。在肾移植患者中所产生的抗ＨＬＡ抗体的频率和ＨＬＡ抗原的分布不同。结论 ＰＲＡ检测对预测移植肾排斥有重要意义。     

他克莫司联合霉酚酸酯应用于胰肾联合移植的初步经验

目的 总结他克莫司(FK506)联合霉酚酸酯(MMF)应用于胰液膀胱引流式胰肾联合移植受者的初步经验. 方法 胰肾联合移植患者14例,术后应用FK506 0.07～0.15mg·kg-1·d-1加MMF 1.0～1.5 g/d加泼尼松25 mg/d三联免疫抑制治疗方案.采用微粒子酶免疫分析法每周测定口服FK506后全血峰谷浓度,依此调整剂量维持最初3个月内FK506全血浓度峰值10～20 μg/L,谷值5～15μg/L.并观察排斥反应的发生及药物的肝肾毒性. 结果 9例患者术后胰肾功能恢复良好,早期无排斥反应发生,血糖及肌酐水平恢复正常.随访18～70个月,平均34个月.存活1～3年者3例,3年～者1例,4年～者1例,>5年者4例,胰肾功能良好,血糖正常,均未使用降糖药.1例因超急性排斥反应术后第2天切除移植胰腺,随访2年肾功能良好.4例死亡,死因分别为术后急性右心功能衰竭、呼吸骤停、急性排斥反应及十二指肠瘘.胰肾联合移植术后各时期FK506全血峰、谷浓度差异均有统计学意义(P<0.05).术后共发生肾脏急性排斥反应4例次,肾毒性2例次,肝毒性1例次. 结论 FK506与MMF在药效上有协同作用,联合应用于胰肾联合移植具有良好的免疫抑制效果,能有效降低排斥反应发生率和提高移植物长期存活率.     

Humoral immunity in renal transplantation: clinical significance and therapeutic approach

Donor-specific antibodies (DSA) form a significant barrier in solid organ transplantation of highly pre-sensitized candidates. Although avoiding transplantation over a positive cross-match test can largely prevent the occurrence of hyperacute antibody-mediated rejection, transplantation of highly pre-sensitized candidates is often complicated by the occurrence of acute and chronic antibody-mediated graft rejection leading to diminished graft function and survival. The pre-existent HLA and/or non-HLA-specific antibodies are without any doubt important contributing factors underlying humoral-mediated graft injury. Furthermore, increasing evidence underlines the association of newly formed de novo DSA after transplantation with poor graft function and survival. There is still a need to further develop desensitizing therapies not only to make transplantation of highly pre-sensitized candidates feasible, but also to reduce the new formation of allo-antibodies. Here, we summarize current views on desensitization therapies and the impact of the presence of DSA on the fate of the kidney graft.     

Significant changes in the alloantibody after lung transplantation in the cyclosporine treated rat model

BACKGROUND: The diagnosis of acute rejection after organ transplantation is often complicated by other possibilities, such as infection. Despite many attempts to identify rejection episodes after transplantation, only the detection of the humoral anti-human leukocyte antigen antibody has been effective in measuring alloimmunization, especially detected with flow cytometry cross-match (FCXM). As an initial step towards gaining a better understanding of the correlation between humoral responses and graft rejection in an immunosuppressant recipient, we investigated responses of alloantibodies (allo-Abs) after lung transplantation (LTx) in a rat model treated with adequate or inadequate cyclosporine A (CsA) therapy. METHODS: Orthotopic LTx was performed using a major histocompatibility complex fully incompatible combination (Brown Norway to Lewis rat). CsA was given subcutaneously to recipients at an optimal or a sub-optimal dosage for 3 days after transplantation. A FCXM technique was used to determine the time-course of changes in titers of allo-Abs in serum. The allo-Ab deposition in the grafted lung was detected with an immunofluorescent staining method. RESULTS: Circulating IgM allo-Ab levels were significantly elevated on day 4 in both groups when histological findings revealed early stage of acute rejection. IgM levels in the sub-optimal dosage group were maximal and significantly higher than those in the optimal dosage group on day 4, and levels then decreased after day 8. IgG allo-Ab levels increased significantly on day 8 and continued to increase throughout the observation period. CONCLUSIONS: Our data suggest that the monitoring IgM allo-Abs might be effective for identifying acute rejection in recipients with inadequate immunosuppression therapy.     

Rotavirus in Organ Transplantation: Drug‐Virus‐Host Interactions

Although rotavirus is usually recognized as the most common etiology of diarrhea in young children, it can in fact cause severe diseases in organ transplantation recipients irrespective of pediatric or adult patients. This comprehensive literature analysis revealed 200 cases of rotavirus infection with 8 related deaths in the setting of organ transplantation been recorded. Based on published cohort studies, an average incidence of 3% (187 infections out of 6176 organ recipients) was estimated. Rotavirus infection often causes severe gastroenteritis complications and occasionally contributes to acute cellular rejection in these patients. Immunosuppressive agents, universally used after organ transplantation to prevent organ rejection, conceivably play an important role in such a severe pathogenesis. Interestingly, rotavirus can in turn affect the absorption and metabolism of particular immunosuppressive medications via several distinct mechanisms. Even though rotaviral enteritis is self‐limiting in general, infected transplantation patients are usually treated with intensive care, rehydration and replacement of nutrition, as well as applying preventive strategies. This article aims to properly assess the clinical impact of rotavirus infection in the setting of organ transplantation and to disseminate the interactions among the virus, host and immunosuppressive medications.