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供者特异性抗体在肝移植中的临床研究

发布时间:2018-11-15 12:21
【摘要】:目的:分析供者特异性抗体(DSA)在肝脏移植受者中的发生率及相关危险因素,及供者特异性抗体对肝移植受者术后移植物功能的影响,并探讨其治疗方法。方法:应用Luminex液相芯片分析平台及LABSScreen R软件对2013年9月至2015年7月收集的139例肝脏移植病例进行HLA(人类白细胞抗原)、群体反应性抗体(PRA),对于PRA阳性病例,继续行DSA、补体C1q、补体C4d及肝脏病理。结果:139例肝脏移植受者中,4例受者术后早期死亡(死亡时间分别为24天、12天、3天、5天),其余受者中位随访周期为15.3月(1.1-29.5月),其中供者特异性抗体(DSA)阴性者127例,阳性者共12例,包括术前受者体内预存DSA(Pre DSA)2例,移植术后新生DSA(dn DSA)10例(其中1例移植术前预存DSA阳性),术后新生DSA发生率为7.19%。移植术前预存DSA2例中,Ⅰ类DSA 1例,基因位点为HLA-A;Ⅱ类DSA1例,基因位点为HLA-DQ;移植术后新发DSA10例,均是Ⅱ类DSA,基因位点均为HLA-DQ。DSA阳性病例中,5例肝脏病理提示肝纤维化、早期急性排斥和胆汁淤积。6例DSA阳性进行C1q检测,其中5例C1q检测提示阳性。FK506(他克莫司)联合甲强龙激素免疫治疗为主的免疫抑制基础上,吗替麦考酚酯的应用降低DSA的形成风险(P=0.017),儿童移植病例中,吗替麦考酚酯(MMF)的应用减少DSA的形成(P=0.025)。91.7%(11/12)DSA阳性受者发生在HLA-DQ基因位点。肝移植术中巴利昔单抗的免疫诱导对DSA的形成无明显影响(P=0.110)。对于DSA阳性病例的治疗选择包括移植术后调整FK506剂量,使移植术后6月内FK506血药浓度维持到目标浓度;DSA阳性病例治疗包括在FK506为免疫抑制剂基础上,同时加用或增加吗替麦考酚酯剂量,或给予甲强龙激素治疗,丙种球蛋白免疫固化等治疗选择。结论:DSA是肝脏移植筛选致敏受者的重要指标,DSA对肝脏移植患者及移植物的预后生存情况存在严重影响,移植术后DSA需密切检测,并根据检查结果及时调整免疫抑制剂方案。
[Abstract]:Objective: to analyze the incidence and risk factors of donor-specific antibody (DSA) in liver transplant recipients and the effect of donor-specific antibody on graft function after liver transplantation. Methods: using Luminex liquid chip analysis platform and LABSScreen R software, 139 liver transplantation cases collected from September 2013 to July 2015 were treated with HLA (Human Leukocyte Antigen). The group reactive antibody (PRA), was used to continue DSA, for PRA positive cases. Complement C 1Q, complement C 4 d and liver pathology. Results: among 139 recipients of liver transplantation, 4 patients died early after operation (24 days, 12 days, 3 days, 5 days, respectively). The median follow-up period of the remaining recipients was 15.3 months (1.1-29.5 months). There were 127 cases of donor specific antibody (DSA) negative and 12 cases of positive, including 2 cases of preexisting DSA (Pre DSA) in recipients and 10 cases of DSA (dn DSA) after transplantation (including 1 case of positive pre-existing DSA before transplantation). The incidence of postoperative DSA was 7.19%. Of the patients with pre-transplantation DSA2, 1 case had class 鈪,

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