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儿童肾移植后早期会出现针对肾脏相关自身抗原(血管紧张素II 1型受体、IV型胶原和纤连蛋白)的抗体的从头发育。

De novo development of antibodies to kidney-associated self-antigens angiotensin II receptor type I, collagen IV, and fibronectin occurs at early time points after kidney transplantation in children.

作者信息

Hesemann Laura E, Subramanian Vijay, Mohanakumar Thalachallour, Dharnidharka Vikas R

机构信息

Division of Pediatric Nephrology, Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, USA.

Department of Surgery, Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA.

出版信息

Pediatr Transplant. 2015 Aug;19(5):499-503. doi: 10.1111/petr.12531. Epub 2015 Jun 9.

DOI:10.1111/petr.12531
PMID:26058970
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4485575/
Abstract

Chronic rejection is the leading cause of graft loss following pediatric kidney transplantation. Our group and others have demonstrated an association between the development of Abs to self-antigens and chronic rejection following adult lung and heart transplantation. The goal of this study was to determine whether Abs to kidney-associated self-antigens develop following pediatric renal transplantation. We investigated post-transplant development of Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, and collagen IV in a pediatric cohort. Using ELISA, we measured Abs to kidney-associated self-antigens in serum. Our cohort included 29 subjects with samples collected pretransplant and for 12 months post-transplant. No samples had Abs to kidney-associated self-antigen pretransplant. In contrast, 50% (10/20) of subjects developed Abs to one or more kidney-associated self-antigen post-transplantation. The median time to antibody appearance and duration of persistence were 103 and 61 days, respectively. Development of Abs did not correlate with graft function. Half of subjects developed Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, or collagen IV in the first year after kidney transplantation--a higher rate of early antibody development than expected. In this small study, Abs did not correlate with worse clinical outcomes.

摘要

慢性排斥反应是小儿肾移植后移植物丢失的主要原因。我们团队及其他研究团队已证明,在成人肺移植和心脏移植后,自身抗体的产生与慢性排斥反应之间存在关联。本研究的目的是确定小儿肾移植后是否会产生针对肾脏相关自身抗原的抗体。我们在一个小儿队列中调查了肾移植后针对肾脏相关自身抗原(血管紧张素II 1型受体、纤连蛋白和IV型胶原)抗体的产生情况。我们使用酶联免疫吸附测定法(ELISA)检测血清中针对肾脏相关自身抗原的抗体。我们的队列包括29名受试者,收集了他们移植前及移植后12个月的样本。移植前没有样本含有针对肾脏相关自身抗原的抗体。相比之下,50%(10/20)的受试者在移植后产生了针对一种或多种肾脏相关自身抗原的抗体。抗体出现的中位时间和持续时间分别为103天和61天。抗体的产生与移植物功能无关。一半的受试者在肾移植后的第一年产生了针对肾脏相关自身抗原血管紧张素II 1型受体、纤连蛋白或IV型胶原的抗体——抗体早期产生率高于预期。在这项小型研究中,抗体与较差的临床结局无关。

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De novo development of antibodies to kidney-associated self-antigens angiotensin II receptor type I, collagen IV, and fibronectin occurs at early time points after kidney transplantation in children.儿童肾移植后早期会出现针对肾脏相关自身抗原(血管紧张素II 1型受体、IV型胶原和纤连蛋白)的抗体的从头发育。
Pediatr Transplant. 2015 Aug;19(5):499-503. doi: 10.1111/petr.12531. Epub 2015 Jun 9.
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本文引用的文献

1
Immune responses to collagen-IV and fibronectin in renal transplant recipients with transplant glomerulopathy.移植性肾小球病肾移植受者对IV型胶原和纤连蛋白的免疫反应。
Am J Transplant. 2014 Mar;14(3):685-93. doi: 10.1111/ajt.12592. Epub 2014 Jan 10.
2
Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies.存在抗血管紧张素 II 型 1 型受体抗体时,肾移植物衰竭的风险增加。
Am J Transplant. 2013 Oct;13(10):2577-89. doi: 10.1111/ajt.12395. Epub 2013 Aug 13.
3
Verification of association of elevated serum IDO enzyme activity with acute rejection and low CD4-ATP levels with infection.验证血清 IDO 酶活性升高与急性排斥反应以及 CD4-ATP 水平降低与感染的相关性。
Transplantation. 2013 Sep;96(6):567-72. doi: 10.1097/TP.0b013e31829c7cec.
4
Alloimmunity-induced autoimmunity as a potential mechanism in the pathogenesis of chronic rejection of human lung allografts.同种异体免疫诱导的自身免疫作为人类肺移植慢性排斥反应发病机制中的一个潜在机制。
J Heart Lung Transplant. 2011 Jun;30(6):624-31. doi: 10.1016/j.healun.2011.01.708. Epub 2011 Mar 16.
5
Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection.自身抗原的抗体使原发性肺移植物功能障碍和慢性排斥反应的易感性增加。
Ann Thorac Surg. 2010 Oct;90(4):1094-101. doi: 10.1016/j.athoracsur.2010.06.009.
6
Subclinical viremia increases risk for chronic allograft injury in pediatric renal transplantation.亚临床病毒血症增加小儿肾移植后慢性移植物损伤的风险。
J Am Soc Nephrol. 2010 Sep;21(9):1579-86. doi: 10.1681/ASN.2009111188. Epub 2010 Jul 8.
7
Viral infection induces de novo lesions of coronary allograft vasculopathy through a natural killer cell-dependent pathway.病毒感染通过自然杀伤细胞依赖性途径诱导冠状动脉移植血管病变的新生病变。
Am J Transplant. 2009 Nov;9(11):2479-84. doi: 10.1111/j.1600-6143.2009.02801.x.
8
New equations to estimate GFR in children with CKD.估算慢性肾脏病儿童肾小球滤过率的新方程。
J Am Soc Nephrol. 2009 Mar;20(3):629-37. doi: 10.1681/ASN.2008030287. Epub 2009 Jan 21.
9
Subclinical cytomegalovirus and Epstein-Barr virus viremia are associated with adverse outcomes in pediatric renal transplantation.亚临床巨细胞病毒和爱泼斯坦-巴尔病毒血症与小儿肾移植的不良预后相关。
Pediatr Transplant. 2007 Mar;11(2):187-95. doi: 10.1111/j.1399-3046.2006.00641.x.
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Viral infection in the renal transplant recipient.肾移植受者中的病毒感染。
J Am Soc Nephrol. 2005 Jun;16(6):1758-74. doi: 10.1681/ASN.2004121113. Epub 2005 Apr 13.