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Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation.手部移植受者体内的非HLA抗体与多次急性排斥反应及内皮细胞活化相关。
J Clin Med. 2022 Feb 4;11(3):833. doi: 10.3390/jcm11030833.
2
Levels of angiotensin II type-1 receptor antibodies and endothelin-1 type-A receptor antibodies correlate with antibody-mediated rejection and poor graft function in kidney-transplantation patients.肾移植患者体内血管紧张素II 1型受体抗体和内皮素-1 A型受体抗体水平与抗体介导的排斥反应及移植肾功能不佳相关。
Transpl Immunol. 2022 Oct;74:101674. doi: 10.1016/j.trim.2022.101674. Epub 2022 Jul 25.
3
Endothelin Type A Receptor Antibodies Are Associated With Angiotensin II Type 1 Receptor Antibodies, Vascular Inflammation, and Decline in Renal Function in Pediatric Kidney Transplantation.内皮素A型受体抗体与小儿肾移植中血管紧张素II 1型受体抗体、血管炎症及肾功能下降相关。
Kidney Int Rep. 2020 Sep 6;5(11):1925-1936. doi: 10.1016/j.ekir.2020.09.004. eCollection 2020 Nov.
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Humoral immunity in hand transplantation: anti-HLA and non-HLA response.手部移植中的体液免疫：抗HLA及非HLA反应。
Hum Immunol. 2014 Aug;75(8):859-62. doi: 10.1016/j.humimm.2014.06.010. Epub 2014 Jun 19.
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Non-HLA Antibodies to G Protein-coupled Receptors in Pediatric Kidney Transplant Recipients: Short- and Long-term Clinical Outcomes.小儿肾移植受者中针对G蛋白偶联受体的非HLA抗体：短期和长期临床结局
Transplantation. 2024 Jan 1;108(1):276-283. doi: 10.1097/TP.0000000000004753. Epub 2023 Dec 13.
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The impact of non-HLA antibodies directed against endothelin-1 type A receptors (ETAR) on early renal transplant outcomes.内皮素-1 型 A 受体（ETAR）非 HLA 抗体对早期肾移植结局的影响。
Transpl Immunol. 2014 Jan;30(1):24-9. doi: 10.1016/j.trim.2013.10.007. Epub 2013 Oct 31.
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Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study.甲襞视频毛细血管镜检查在心脏移植受者中对微循环的无创评估以及与内皮功能障碍、心血管危险因素和非HLA抗体的预后相关性：一项初步研究
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The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes.针对血管紧张素II 1型受体（AT1R）的非HLA抗体对肾移植早期结局的影响。
Transpl Int. 2014 Oct;27(10):1029-38. doi: 10.1111/tri.12371. Epub 2014 Jun 30.
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Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients.非 HLA 激动性抗血管紧张素 II 型 1 受体抗体在肾移植受者中诱导独特的抗体介导排斥反应表型。
Kidney Int. 2019 Jul;96(1):189-201. doi: 10.1016/j.kint.2019.01.030. Epub 2019 Mar 15.
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Non-HLA antibodies: angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) are associated with renal allograft injury and graft loss.非HLA抗体：血管紧张素II 1型受体（抗AT1R）和内皮素-1 A型受体（抗ETAR）与肾移植损伤及移植肾丢失相关。
Transplant Proc. 2014 Oct;46(8):2618-21. doi: 10.1016/j.transproceed.2014.09.029.

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The Influence of Anti-PAR 1 and Anti-ACE 2 Antibody Levels on the Course of Specific Glomerulonephritis Types.抗PAR 1和抗ACE 2抗体水平对特定类型肾小球肾炎病程的影响。
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The Influence of Anti-ETAR and Anti-CXCR3 Antibody Levels on the Course of Specific Glomerulonephritis Types.抗内皮素受体A和抗CXC趋化因子受体3抗体水平对特定类型肾小球肾炎病程的影响
J Clin Med. 2024 Dec 19;13(24):7752. doi: 10.3390/jcm13247752.
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Impact of everolimus plus calcineurin inhibitor on formation of non-HLA antibodies and graft outcomes in kidney transplant recipients: 12-month results from the ATHENA substudy.依维莫司联合钙调神经磷酸酶抑制剂对肾移植受者非HLA抗体形成及移植结局的影响：ATHENA子研究的12个月结果
Front Transplant. 2023 Nov 21;2:1273890. doi: 10.3389/frtra.2023.1273890. eCollection 2023.
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Autoantibodies from patients with kidney allograft vasculopathy stimulate a proinflammatory switch in endothelial cells and monocytes mediated via GPCR-directed PAR1-TNF-α signaling.来自于肾移植血管病患者的自身抗体通过 GPCR 靶向 PAR1-TNF-α 信号转导，刺激内皮细胞和单核细胞中的促炎转换。
Front Immunol. 2023 Oct 30;14:1289744. doi: 10.3389/fimmu.2023.1289744. eCollection 2023.
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Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study.甲襞视频毛细血管镜检查在心脏移植受者中对微循环的无创评估以及与内皮功能障碍、心血管危险因素和非HLA抗体的预后相关性：一项初步研究
J Clin Med. 2023 Mar 16;12(6):2302. doi: 10.3390/jcm12062302.
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Chronic Active T-Cell Mediated Kidney Rejection as a Clinically Significant Type of Allograft Loss?慢性活动性T细胞介导的肾移植排斥反应是一种具有临床意义的移植肾丢失类型吗？
Diagnostics (Basel). 2022 Dec 19;12(12):3220. doi: 10.3390/diagnostics12123220.
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Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies.抗原和基于细胞的检测方法用于非 HLA 抗体的检测。
Front Immunol. 2022 May 6;13:864671. doi: 10.3389/fimmu.2022.864671. eCollection 2022.

本文引用的文献

1
The role of endothelin II type A receptor (ETAR) in transplant injury.内皮素 II 型受体（ETAR）在移植损伤中的作用。
Transpl Immunol. 2022 Feb;70:101505. doi: 10.1016/j.trim.2021.101505. Epub 2021 Nov 15.
2
Novel allosteric ligands of the angiotensin receptor AT1R as autoantibody blockers.血管紧张素受体 AT1R 的新型别构配体作为自身抗体阻断剂。
Proc Natl Acad Sci U S A. 2021 Aug 17;118(33). doi: 10.1073/pnas.2019126118.
3
Endothelin A Receptors Expressed in Glomeruli of Renal Transplant Patients May Be Associated with Antibody-Mediated Rejection.肾移植患者肾小球中表达的内皮素A受体可能与抗体介导的排斥反应有关。
J Clin Med. 2021 Jan 22;10(3):422. doi: 10.3390/jcm10030422.
4
Abnormal Nailfold Capillaries in Patients after Hand Transplantation.手部移植术后患者的甲襞毛细血管异常
J Clin Med. 2020 Oct 25;9(11):3422. doi: 10.3390/jcm9113422.
5
The role of non-HLA antibodies in solid organ transplantation: a complex deliberation.非 HLA 抗体在实体器官移植中的作用：一个复杂的考量。
Curr Opin Organ Transplant. 2020 Dec;25(6):536-542. doi: 10.1097/MOT.0000000000000811.
6
TNF, IL-6, and IL-10 cytokines levels and their polymorphisms in renal function and time after transplantation.TNF、IL-6 和 IL-10 细胞因子水平及其在肾功能和移植后时间的多态性。
Immunol Res. 2020 Oct;68(5):246-254. doi: 10.1007/s12026-020-09147-3.
7
The significance of angiotensin II type 1 receptor (AT1 receptor) in renal transplant injury.血管紧张素 II 型 1 型受体 (AT1 受体) 在肾移植损伤中的意义。
Adv Clin Exp Med. 2020 May;29(5):629-633. doi: 10.17219/acem/121510.
8
Angiotensin II Type 1 Receptor Expression in Renal Transplant Biopsies and Anti-AT1R Antibodies in Serum Indicates the Risk of Transplant Loss.肾移植活检中血管紧张素II 1型受体表达及血清中抗AT1R抗体提示移植肾丢失风险。
Transplant Proc. 2020 Oct;52(8):2299-2304. doi: 10.1016/j.transproceed.2020.01.126. Epub 2020 May 21.
9
Rejection in the setting of non-HLA antibody: New tools for navigating bench to bedside.
Am J Transplant. 2020 Oct;20(10):2639-2641. doi: 10.1111/ajt.15975. Epub 2020 May 25.
10
Humoral Alloreactivity in VCA Recipients: Should We Learn From Our Experience?血管细胞黏附分子-1 受体抗体阳性受者的体液性同种异体反应性：我们是否应该吸取经验教训？
Transplantation. 2020 Oct;104(10):2003-2010. doi: 10.1097/TP.0000000000003164.

手部移植受者体内的非HLA抗体与多次急性排斥反应及内皮细胞活化相关。

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation.

作者信息

Sikorska Dorota, Kamińska Dorota, Catar Rusan, Banasik Mirosław, Heidecke Harald, Schulze-Forster Kai, Korybalska Katarzyna, Rutkowski Rafał, Łuczak Joanna, Jabłecki Jerzy, Oko Andrzej, Daroszewski Przemysław, Kusztal Mariusz, Samborski Włodzimierz

机构信息

Department of Rheumatology, Rehabilitation and Internal Medicine, Poznan University of Medical Sciences, 61-545 Poznan, Poland.

Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wroclaw, Poland.

出版信息

J Clin Med. 2022 Feb 4;11(3):833. doi: 10.3390/jcm11030833.

DOI:10.3390/jcm11030833
PMID:35160284
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8837026/
Abstract

The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

摘要

抗人白细胞抗原（HLA）抗体在移植排斥反应中的作用已广为人知，但与非HLA抗体相关的损伤目前也受到广泛讨论。我们研究的目的是调查非HLA抗体在手部同种异体移植排斥反应中的作用。该研究对6例手部移植术后患者进行。对照组包括：12例肾移植受者和12名健康志愿者。检测了以下非HLA抗体：抗血管紧张素II 1型受体抗体（AT1R-Ab）、抗内皮素-1 A型受体抗体（ETAR-Ab）、抗蛋白酶激活受体1抗体（PAR-1-Ab）和抗血管内皮生长因子A抗体（VEGF-A-Ab）。选用促炎细胞因子（Il-1、IL-6、IFNγ）来评估移植后的体液反应。使用内皮激活的实验室标志物（VEGF、sICAM、vWF）来评估潜在的血管病变。急性排斥反应次数最多的患者同时具有阳性非HLA抗体：AT1R-Ab和ETAR-Ab。同一患者的VEGF-A-Ab水平最高，PAR1-Ab水平也非常高。所有手部移植术后患者的内皮激活实验室标志物水平都很高。手部移植术后患者中观察到的非HLA抗体的存在以及多次急性排斥反应，应促使人们去探寻非HLA抗体在血管复合组织异体移植体液损伤中的潜在作用。