发展中国家以淋巴细胞耗竭为基本策略的活体肾移植耐受方案。

Sufi M Suhail
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摘要

终末期肾衰竭(ESKD)是一个全球性问题,肾脏替代疗法给发展中国家人民带来了巨大的经济负担,此外血液透析和腹膜透析技术的可用性也受到严重限制。肾移植的最佳选择还需要终身联合免疫抑制药物,其费用与终身透析相当。实现移植耐受的策略需要最少的免疫抑制药物,尽管处于实验阶段,但也需要最先进的技术和昂贵的药物和干预措施。这显然超出了发展中国家ESKD患者的承受能力。因此,在全球发展中国家,迫切需要一种创新但具有成本效益的耐受方案,这是成功移植计划的迫切需要。简而言之,移植耐受被定义为供体对同种异体抗原的特异性无反应状态,无需持续的药物免疫抑制或最低限度的需要。目前最先进的技术包括:(1)血液嵌合体状态,用于完全耐受;(2)单克隆抗体抑制免疫反应性t淋巴细胞的适当或部分耐受;(3)嵌合抗原受体用于t -调节(T-reg)细胞治疗,利用基因工程T-reg细胞靶向特异性t淋巴细胞受体诱导能量。根据我们在移植后淋巴增殖性疾病(PTLD)的移植管理方面的实际经验,我们注意到在PTLD的淋巴消融治疗后,免疫抑制药物的需求经常急剧减少。我们最近发表了一个真实世界移植案例的案例研究,其中我们解释了淋巴细胞消融治疗后产生的部分或适当耐受性,随后使用低剂量双标准免疫抑制药物维持同种异体移植物。在此基础上,我们提出了一种创新的发展中国家低风险活体肾移植耐受方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Tolerance protocol of living kidney transplant for developing countries through basic strategy of lymphocyte depletion.

End-stage kidney failure (ESKD) is a global issue where kidney replacement therapy imposes enormous economic burden to people of developing countries, in addition to the severe limitations to the availability of hemodialysis and peritoneal dialysis technique. The best option of kidney transplantation also requires lifelong combination immunosuppressive medicines, the cost of which is equally comparable to lifelong dialysis. A strategy of achieving transplant tolerance that requires minimum immunosuppressive medicines, although in experimental stage, also requires state-of-art technology with costly medicines and interventions. This is evidently beyond the reach of ESKD patients of developing countries. Hence, globally in developing countries, a need for an innovative but cost-effective tolerance protocol is a burning need for a successful transplant program. In brief, transplant tolerance is defined as a state of donor-specific unresponsiveness to the allograft antigens without the need for ongoing pharmacologic immunosuppression or with a minimal need. Current state-of-art techniques involves: (1) A state of hematological chimera, for complete tolerance; (2) Prope or partial tolerance where immune-reactive T-lymphocytes are inhibited using monoclonal antibodies; and (3) Chimeric antigen receptor for T-regulatory (T-reg) cell therapy using genetically engineered T-reg cells targeting specific T-lymphocyte receptors for inducing anergy. From our real-world experience in transplant management in post-transplant lympho-proliferative disorders (PTLD), we noticed frequently a drastic reduction in the need of immunosuppressive medicines following lympho-ablative therapy for PTLD. We recently published a case study on a real-world experience transplant case where we explained a partial or prope tolerance that developed after lymphocyte ablation therapy, following which the allograft was maintained with low dose dual standard immunosuppressive medicines. Based on this publication, we propose here an innovative tolerance protocol for living related low risk kidney transplantation for developing countries, in this opinion review.

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