抗体介导的移植肾排斥反应的治疗进展

随着C4d免疫染色和抗供体特异性抗体(DSA)检测技术的不断发展,抗体介导的排斥反应(AMR)对肾移植后移植肾存活的影响越来越受到重视,相对于细胞性排斥反应,AMR对常规的抗排斥治疗普遍缺乏敏感,预后也较急性细胞性排斥反应差.近年血浆分离(PP)/血浆置换(PE)/免疫吸附(IA)、静脉免疫球蛋白(IVIG)、利妥昔单抗联合治疗和新的免疫抑制剂的应用,AMR的临床治疗取得了显著成效,但最佳方案仍需要进一步评价.     

移植肾急性排斥组织中C4d CD3 CD4 CD8 CD138表达的初步研究

目的分析探讨移植肾急性排斥组织中C4d、CD3、CD4、CD8、CD138的表达。方法收集我院2010年3月至2013年10月经病理学确认为急性排斥反应移植肾穿刺标本136例,依据Banff 2007标准将研究对象分为5组,利用免疫组织化学染色计数测定各组C4d、CD3、CD4、CD8、CD138阳性表达情况并计算CD4/CD8值。结果急性抗体介导性排斥反应组C4d染色均为阳性,急性T细胞介导性排斥反应组C4d染色均为阴性;CD3、CD4、CD8阳性细胞数及CD4+/CD8+值急性T细胞介导性排斥反应组高于急性抗体介导性排斥反应组,差异有统计学意义(P<0.01),急性T细胞性排斥Ⅰ、Ⅱ级组高于疑为急性T细胞介导性排斥组,差异有统计学意义(P<0.01),急性T细胞性排斥Ⅱ级组高于急性T细胞性排斥Ⅰ级组,差异具有统计学意义(P<0.05),急性抗体介导性排斥反应Ⅰ级组与急性抗体介导性排斥反应Ⅱ级组差异无统计学意义(P>0.05);CD138阳性细胞急性抗体介导性排斥反应组大于急性T细胞介导性排斥反应组,差异有统计学意义(P<0.01),急性抗体介导性排斥反应Ⅱ级组高于急性抗体介导性排斥反应Ⅰ级组,差异具有统计学意义(P<0.05),急性T细胞介导性排斥反应3组比较,差异无统计学意义(P>0.05)。结论 C4d的表达和CD3、CD4、CD8、CD138阳性细胞数以及CD4+/CD8+值与肾移植急性排斥反应的类型及反应程度密切相关,检测C4d、CD3、CD4、CD8、CD138在移植肾急性排斥组织中表达情况,对于探讨移植肾早期急性排斥反应发生具有重要意义。     

人类白细胞抗原误配与肾移植术后早期排斥反应

<正>对于慢性肾功能衰竭和尿毒症的患者,肾移植是目前临床治疗该类疾病的重要方法。人类白细胞抗原(HLA)与同种异体的器官移植中发生的排斥反应密切相关。HLA分型血清     

整合素连接激酶在抗体介导的慢性排斥反应患者肾组织中的表达及意义

目的研究移植肾组织中整合素连接激酶(ILK)及Ⅳ型胶原、转化生长因子β1(TGF-β1)表达和抗体介导的慢性排斥反应的关系。方法 用免疫组织化学技术和计算机真彩色图像分析系统半定量检测46例抗体介导的慢性排斥反应(Chronic active antibody-mediated rejection,ABMR)患者移植肾组织中ILK、Ⅳ型胶原和TGF-β1的表达情况,分析3者间及与ABMR的间质纤维化与肾小管萎缩(IF/TA)的病理分级之间的关系。15例正常肾组织作为对照。结果 ABMR移植肾组织中ILK、Ⅳ型胶原、TGF-β1的表达比正常肾组织明显增加(P<0.001),并随ABMR中IF/TA病理分级呈逐渐递增的趋势。移植肾组织中ILK的表达与TGF-β1、Ⅳ型胶原呈正相关(r分别为0.830、0.707,P<0.001)。结论 ILK可能是介导TGF-β1促进移植肾间质纤维化细胞外基质(extracellular matrix,ECM)异常沉积的发病机制,Ⅳ型胶原的异常沉积是ABMR中IF/TA患者移植肾纤维化的重要表现。转化生长因子β1已经证明了与移植肾纤维化显著的相关性,ILK在抗体介导的排斥反应的移植肾纤维化进程中起重要作用。     

硼替佐米对大鼠肾移植AMR的保护作用及机制研究

目的研究硼替佐米对肾移植抗体介导排斥反应(AMR)的保护作用及机制。方法采用输血致敏法构建大鼠肾移植AMR模型。在此模型基础上,静脉注射硼替佐米,研究其对移植肾功能和病理损害的保护作用。流式细胞仪检测供体特异性抗体(DSA)的水平,免疫组织化学检测移植肾C4d表达,免疫荧光法检测CD68表达以反映巨噬细胞的浸润。结果硼替佐米可以明显改善肾移植AMR大鼠移植肾功能(P<0.05),减轻移植肾病理损害。硼替佐米显著降低大鼠肾移植AMR模型血清中IgM、IgG 2b和IgG 2c等DSA亚型的水平(P<0.05),同时抑制移植肾组织中C4d的表达和巨噬细胞浸润。结论硼替佐米对肾移植AMR具有明显的保护作用,其机制可能与抑制受体DSA产生及减少移植肾组织中巨噬细胞浸润有关。     

Emerging drugs for prevention of T-cell mediated rejection in liver and kidney transplantation

Introduction: Acute and chronic graft rejection continues to be an important problem after solid organ transplantation. With the introduction of potent immunosuppressive agents such as calcineurin inhibitors, the risk of rejection has been significantly reduced. However, the adverse effects of life-long immunosuppression remain a concern, and there exist a fine balance between over-immunosuppression and risk of rejection.

Areas covered: In this review, the current standard of care in immunosuppressive therapy, including the use of steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of rapamycin inhibitors, will be discussed. Newer immunosuppressive agents showing promising early data after liver and kidney transplantation will also be explored.

Expert Opinion: Currently, calcineurin inhibitors continue to be a vital component of immunosuppressive therapy after solid organ transplantation. Although minimization and avoidance strategies have been developed, the ultimate goal of inducing tolerance remains elusive. Newer emerging agents should have potent and specific immunosuppressive activity, with minimal associated side effects. An individualized approach should be adopted to tailor immunosuppression according to the different needs of recipients.     

气管、隆突支气管患者围手术期护理

目的对气管支气管患者围手术期的护理经验进行总结。方法 48例气管支气管围手术期患者中24例进行常规普通护理;另24例患者术前进行有针对性护理,急诊气管支气管外伤患者处理及时,术后密切观察生命体征,加强胸腔闭式引流管护理,保持呼吸道通畅,协助患者有效咳嗽和排痰,以及对患者的疼痛、卧位及并发症采取相应的护理措施。结果围手术期24例普通护理患者中1例死亡,8例出现并发症;围手术期24例针对性护理患者中未出现并发症。普通护理患者平均住院天数为(29±15)d,针对性护理患者为(18±6)d。结论高质量的术前、术后护理能加快气管支气管患者的康复,降低手术患者的术后并发症,减轻患者的经济负担,是手术成功及患者平稳恢复的重要保障。     

巴利昔单抗在预防肾移植后排斥反应中的应用

目的:探讨巴利昔单抗诱导治疗预防肾移植后急性排斥反应的有效性和安全性。方法:在使用环孢素、霉酚酸酯及激素三联抗排斥的基础上,将42例肾移植受者随机分2组,每组各21例,试验组术前30min及术后d4各给予巴利昔单抗20mg+氯化钠注射液100mL,静脉滴注,对照组只使用氯化钠注射液静脉滴注。评价急性排斥反应的发生率、严重程度以及巴利昔单抗治疗的安全性。结果:试验组急性排斥反应发生率10%(2/21),发生时间(2.8±s0.8)mo;对照组发生率29%(6/21),发生时间(1.1±0.7)mo,早于试验组(P<0.01)且严重程度高于试验组。血肌酐恢复正常的时间试验组(4.0±0.7)d,对照组(7.8±1.6)d,P<0.01。不良反应发生率2组间差异无显著意义,P<0.05。结论:巴利昔单抗联合环孢素、霉酚酸酯和激素预防肾移植后急性排斥反应安全有效。     

Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection

The prevention of xenograft rejection is substantially dependent on inhibiting antibodies (Ab) produced by B-cells independently of T-cell signals (TI-1). Due to their ubiquitous biochemical mechanisms of action, the immunosuppressants currently employed not only fail to discriminate between B- and T-cells but also have a narrow therapeutic window and, thus, their prolonged use in complex immunosuppressive regimens is problematic. By capitalizing on the target enzyme-bound (DHODH) structure 1b of one of these compounds, leflunomide, and modulating part of its multiple mechanisms of action to gain selectivity, the quinoline-8-carboxamide 3 was designed as a potentially weak enzyme inhibitor but effective immunosuppressant. Compound 3 fulfilled the mechanistic criteria set and had 10-fold B-cell over T-cell selectivity. Its pyridyl analogue 4 was found to be a highly potent and selective B-cell immunosuppressant with a 75-fold selectivity for B- over T-cells (as judged by the MLR data) and no general cytotoxicity at concentrations up to 160-fold higher than those required to inhibit B-cells. In the mouse, 4 effectively blocked TI-1 Ab production and suppressed Ab-mediated xenograft rejection in a xenotransplantation model under a once-daily dosing regimen, with efficacy down to 0.3 mg/kg/day po. These are the first data demonstrating the feasibility of the development of drugs specific for impeding Ab production.     

肾移植患者MRP2C3972T基因多态性对吗替麦考酚酯药动学参数、不良反应及急性排斥反应的影响

目的：研究MRP2 C3972T基因突变对肾移植术后患者服用吗替麦考酚酯药动学参数.不良反应及急性排斥反应的影响.方法：采用聚合酶链反应（PCR）和限制性内切片段长度多态性（RFLP）方法检测肾移植患者MRP2 C3972T基因型,比较不同基因型患者之间吗替麦考酚酯的药动学参数.不良反应及急性排斥反应发生率的差异.结果：肾移植术后第7天.第14天.第30天各基因型患者在C0、C0/D、AUC0-12、AUC0-12/D等值上没有显著性差异,但突变型患者（C/C＋T/T）在术后第7天、第14天、第30天的C0/D、AUC0-12/D均低于野生型（C/C）患者.三组间不良反应及急性排斥反应发生率没有显著差异.结论：MRP2C3972T突变可以在一定程度上降低血浆中麦考酚酸的浓度.     

优质护理在胸外科患者围手术期的应用效果

目的:分析胸外科患者围手术期优质护理的应用效果.方法:按照就诊顺序编号将87例患者分为两组,观察组44例行优质护理,对照组43例行常规护理,对比两组患者护理效果.结果:观察组SAS评分较对照组明显降低,护理满意度95.5％较对照组74.4％明显提高(P＜0.05).结论:胸外科患者围手术期采取优质护理,可明显提高手术质量,缓解患者负性情绪.     

Role of altered prednisolone-specific lymphocyte sensitivity in chronic renal failure as a pharmacodynamic marker of acute allograft rejection after kidney transplantation

Summary The effects of four immunosuppressive agents on the in vitro blastogenesis of peripheral blood lymphocytes activated by concanavalin A have been studied using cells from 26 healthy subjects, 34 patients with chronic renal failure (CRF) and 30 kidney transplant recipients.Differences in lymphocyte sensitivity to prednisolone between the healthy subjects and the CRF patients were statistically significant (P<0.0002), with impaired sensitivity in CRF. Impaired lymphocyte sensitivity occurred in 3.8% and 52.9% of the healthy and CRF subjects, respectively. Lymphocyte sensitivity to prednisolone, both preoperatively and 3 months post-operatively, was strongly correlated with early allograft rejection during co-administration of prednisolone with cyclosporin or azathioprine. Lymphocyte sensitivity to cyclosporin, azathioprine, and mizoribine in CRF was not significantly less than that in healthy subjects.Since the pharmacokinetics of prednisolone are little altered in renal transplantation, it is concluded that lymphocyte sensitivity specific to prednisolone may be a pharmacodynamic marker characteristic of successful graft survival in patients with histo-incompatibility and/or drug resistance.     

Comparison of azathioprine and mycophenolate mofetil for the prevention of acute rejection in recipients of pancreas transplantation

The study was performed to compare the efficacy and side effects of azathioprine (AZA) and mycophenolate mofetil (MMF) in conjunction with cyclosporine or tacrolimus and steroids for the prevention of acute pancreas rejection during the first 6 months of pancreas transplantation. In this case-controlled study, MMF is compared with historical controls of AZA in the prevention of acute pancreas rejection. The primary measures of treatment efficacy were patient and pancreas survival rate at 6 months after transplantation. Secondary efficacy measures were the occurrence of biopsy-proven pancreas rejections and the use of antilymphocyte preparations for rejection treatment. A total of 111 pancreas transplant patients (57 in the AZA group and 54 in the MMF group) were evaluated. The 6-month patient survival rate was 96% in the AZA group versus 97% in the MMF group (p = 0.57). The 6-month pancreas graft survival rate was 88% in the AZA group versus 91% in the MMF group (p = 0.29). However, biopsy-proven rejection episodes during the first 6 months of transplantation were significantly lower with MMF (46%) than with AZA (69%) (p = 0.01). In addition, patients in the AZA group received a greater number of full courses of antilymphocyte therapy as a rejection treatment (p = 0.004). Overall, the frequency of adverse events was similar, although the MMF group experienced higher incidences of gastrointestinal adverse events. In conclusion, compared with AZA, MMF significantly reduces the rate of biopsy-proven pancreas rejection during the first 6 months of transplantation and is well tolerated, except for gastrointestinal adverse events.     

术后时间不同的肾移植受者生活质量影响因素分析

目的 分析术后时间不同的肾移植受者生活质量的水平及其影响因素.方法 采用一般资料问卷、生活质量评价简明量表、疾病进展恐惧简化量表、医学应对方式问卷、肾移植自我管理量表、感恩问卷、领悟社会支持量表、侵扰性思想量表、心理困扰、医院焦虑抑郁量表对2019年7—11月在安徽省立医院肾移植门诊随访的345例肾移植受者进行问卷调查,并按照术后时间(<1年,1～3年,>3～5年,>5年)分组,比较生活质量及影响因素差异.结果 共收回有效问卷323份.生活质量生理总分为(49.83±7.72)分,心理总分为(49.54±9.43)分.不同术后时间(<1年,1～3年,>3～5年,>5年)的生理总分和心理总分呈现动态变化[生理总分:(50.16±7.39)分比(49.65±7.62)分比(53.11±6.88)分比(44.25±8.39)分;心理总分:(50.20±9.03)分比(49.11±10.10)分比(51.90±8.99)分比(43.95±8.27)分,均P<0.05].年龄、月收入、是否发生感染、疾病进展恐惧感是肾移植受者生活质量生理总分影响因素(P<0.05),性别、是否再入院、感恩、心理困扰、应对方式、社会支持、焦虑、抑郁等是不同术后时间肾移植受者生活质量心理总分的影响因素(P<0.05).结论 肾移植受者的生活质量水平随着术后时间的推移呈现动态变化,且在不同术后时间段生活质量的影响因素亦不同,包括年龄、月收入、性别、是否再入院等.