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Rapid reduction of high-level pre-formed donor-specific antibodies after simultaneous liver-kidney transplantation: a report of two cases.
BMC Nephrology ( IF 2.3 ) Pub Date : 2020-02-12 , DOI: 10.1186/s12882-020-01714-y
Christina Lai 1, 2, 3 , Allyson Newman 1, 3 , Jane Mawson 1, 3 , Frederika Abou-Daher 4 , Narelle Watson 4 , Avik Majumdar 5, 6 , Kate Wyburn 1, 2, 3, 6 , Steve Chadban 1, 2, 3, 6 , David Gracey 1, 2, 3, 6
Affiliation  

BACKGROUND Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required. CASE PRESENTATION Two patients underwent SLKT and received our centre's standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant. CONCLUSIONS These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.

中文翻译:

同时进行肝肾移植后快速减少高水平预先形成的供体特异性抗体:两例报道。

背景技术在高滴度供体特异性抗体(DSA)存在下进行的肾脏移植可能会导致超急性或加速的抗体介导的排斥反应和同种异体移植的快速丧失。先前的研究表明,同时进行肝肾移植(SLKT)可以减轻这种风险。但是,机制还没有很好地定义。在这里,我们报告了两名高敏感性SLKT接受者围手术期预形成的高水平DSA的演变,并描述了从肝脏吻合之日起所有DSA的持续严重耗竭,而无需进行额外的脱敏治疗。病例介绍2例患者接受了SLKT,并接受了本中心的标准肾移植免疫抑制治疗,其中巴利昔单抗和甲基泼尼松龙用于诱导治疗,泼尼松龙用于治疗,霉酚酸酯和他克莫司用于维持治疗。术前收集HLA抗体样品,并在肝和肾后血运重建后立即收集,然后在移植后定期收集。还进行了补体依赖性细胞毒性(CDC)交叉匹配。两名患者对PRA的敏感度均超过97%。一名患者在移植前B细胞和T细胞交叉匹配阳性。这些阳性的CDC交叉匹配变为阴性,并且在肝脏血运重建后3小时内,预先形成的DSA的水平急剧而迅速地降低。肝脏异种移植后,即刻植入肾脏同种异体移植物后,无论亚类如何,预形成的DSA均减少。没有观察到非供体特异性HLA抗体的显着减少。两名患者均保持良好的移植物功能,移植后10周进行的肾脏同种异体移植活检没有排斥反应。结论这些病例支持在SLKT背景下肝脏的保护性免疫调节作用,而对于这些高度敏感的患者,术前未给予额外的脱敏治疗。
更新日期:2020-02-12
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