Complement-targeted therapies in kidney transplantation-insights from preclinical studies.
Complement-targeted therapies in kidney transplantation-insights from preclinical studies.
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DOI：
10.3389/fimmu.2022.984090
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发表时间：
2022
影响因子：
7.3
通讯作者：
Kwun, Jean
中科院分区：
文献类型：
--
作者：
Anwar, Imran J.;DeLaura, Isabel;Ladowski, Joseph;Gao, Qimeng;Knechtle, Stuart J.;Kwun, Jean
补体系统的异常激活导致实体器官移植物功能障碍和衰竭。在肾移植中，补体系统与抗体和细胞介导的排斥反应、缺血-再灌注损伤和血管损伤的发病机制有关。这导致了对选择的补体抑制剂（例如，C1和C5抑制剂）的临床试验结果喜忧参半。然而，补体系统是高度复杂的：它是由50多个液相和表面结合的元素，包括几个补体激活受体-所有潜在的治疗目标，在肾移植。靶向药物的产生和基因编辑工具的使用使人们更好地理解了同种和异种移植中补体系统的复杂性。这篇综述总结了我们目前对补体系统在肾移植排斥反应中的作用的认识，特别是回顾了从临床前模型（啮齿动物和非人灵长类动物）中获得的可能转化为临床试验的证据。
Aberrant activation of the complement system contributes to solid-organ graft dysfunction and failure. In kidney transplantation, the complement system is implicated in the pathogenesis of antibody- and cell-mediated rejection, ischemia-reperfusion injury, and vascular injury. This has led to the evaluation of select complement inhibitors (e.g., C1 and C5 inhibitors) in clinical trials with mixed results. However, the complement system is highly complex: it is composed of more than 50 fluid-phase and surface-bound elements, including several complement-activated receptors—all potential therapeutic targets in kidney transplantation. Generation of targeted pharmaceuticals and use of gene editing tools have led to an improved understanding of the intricacies of the complement system in allo- and xeno-transplantation. This review summarizes our current knowledge of the role of the complement system as it relates to rejection in kidney transplantation, specifically reviewing evidence gained from pre-clinical models (rodent and nonhuman primate) that may potentially be translated to clinical trials.
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影响因子：
5.4
作者：
DANIELSSON, C;PASCUAL, M;SCHIFFERLI, JA
通讯作者：
SCHIFFERLI, JA
影响因子：
8.8
作者：
Eskandary, F.;Jilma, B.;Boehmig, G. A.
通讯作者：
Boehmig, G. A.
DOI：
10.1007/978-1-4614-4118-2_4
发表时间：
2013-01-01
期刊：
COMPLEMENT THERAPEUTICS
影响因子：
--
作者：
Das, Nibhriti;Biswas, Bintili;Khera, Rohan
通讯作者：
Khera, Rohan
影响因子：
20.1
作者：
Brunn, GJ;Saadi, S;Platt, JL
通讯作者：
Platt, JL
影响因子：
3.9
作者：
Estrada JL;Martens G;Li P;Adams A;Newell KA;Ford ML;Butler JR;Sidner R;Tector M;Tector J
通讯作者：
Tector J