Antibodies against Angiotensin II Type 1 and Endothelin A Receptors: Relevance and pathogenicity.
Antibodies against Angiotensin II Type 1 and Endothelin A Receptors: Relevance and pathogenicity.
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DOI：
10.1016/j.humimm.2019.04.012
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发表时间：
2019-08
期刊：
影响因子：
2.7
通讯作者：
Fedarko N
中科院分区：
文献类型：
--
作者：
Philogene MC;Johnson T;Vaught AJ;Zakaria S;Fedarko N
抗两种G蛋白偶联受体(GPCRs)、血管紧张素II 1型受体(AT1R)和内皮素A受体(ETAR)的抗体是越来越多的与移植物功能障碍有关的自身抗体之一。AT1R抗体(AT1Rabs)和ETARabs(ETARabs)被证明可以激活它们的靶受体并影响信号通路。多个单中心报告表明，在肾、心、肝、肺和复合组织移植中，这些抗体的存在与急性或慢性排斥反应和移植物丢失之间存在关联。然而，最有可能出现不良结果的患者的特征，仅由这些抗体引起的移植物损伤的表型，以及导致功能障碍所需的抗体效价仍然是有争议的领域。这篇综述汇编了关于抗GPCRs抗体在其他疾病中的作用的现有知识，以弥合移植生物学中的知识差距。强调了未来的研究领域，包括需要对使用AT1Rabs和ETARabs的移植患者进行功能分析和治疗方案。了解激活GPCRs的抗体如何影响移植结果将对移植候选者的先发制人评估以及器官接受者的移植后护理具有直接的临床意义。
Antibodies against two G-protein coupled receptors (GPCRs), angiotensin II type 1 receptor (AT1R) and endothelin A receptor (ETAR) are among a growing number of autoantibodies that are found to be associated with allograft dysfunction. AT1R antibodies (AT1Rabs) and ETAR antibodies (ETARabs) have been shown to activate their target receptors and affect signaling pathways. Multiple single center reports have shown an association between presence of these antibodies and acute or chronic rejection and graft loss in kidney, heart, liver, lung and composite tissue transplantations. However, the characteristics of patients that are most likely to develop adverse outcomes, the phenotypes associated with graft damage solely due to these antibodies, and the antibody titer required to cause dysfunction are areas that remain controversial. This review compiles existing knowledge on the effect of antibodies against GPCRs in other diseases in order to bridge the gap in knowledge within transplantation biology. Future areas for research are highlighted and include the need for functional assays and treatment protocols for transplant patients who present with AT1Rabs and ETARabs. Understanding how antibodies that activate GPCRs influence transplantation outcome will have direct clinical implications for pre-emptive evaluation of transplant candidates as well as the post-transplant care of organ recipients.
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