Chronic humoral rejection of human kidney allografts associates with broad autoantibody responses.
Chronic humoral rejection of human kidney allografts associates with broad autoantibody responses.
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DOI：
10.1097/tp.0b013e3181d72091
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发表时间：
2010-05-27
期刊：
影响因子：
6.2
通讯作者：
Zorn E
中科院分区：
文献类型：
--
作者：
Porcheray F;DeVito J;Yeap BY;Xue L;Dargon I;Paine R;Girouard TC;Saidman SL;Colvin RB;Wong W;Zorn E
慢性体液性排斥反应是肾移植术后的主要并发症。目前尚不清楚引起腹泻的原因。在肾移植受者中经常报告自身抗体以及抗供体人类白细胞抗原抗体。然而，缺乏全面的研究，限制了我们的理解，这种自身免疫性成分的病理生理学CHR。通过使用一系列的ELISA和免疫细胞化学检测，我们评估了自身抗体的发展，在25例肾移植受者与肾功能稳定的25例移植功能。我们还比较了5个cardiac和5个非cardiac患者血清与8027重组人蛋白质的蛋白质芯片的反应性。我们观察到，大多数的AML患者，而不是非AML对照患者，在排斥反应发生时，对一种或几种自身抗原产生了抗体反应。蛋白质微阵列分析显示，在CHR的时候，爆发的自身免疫。值得注意的是，微阵列分析显示，最小的重叠之间的配置文件，表明每个cardiovascular患者已经开发了一套独特的抗原靶标的自身抗体。自身抗体反应的广度，加上缺乏共识的目标，表明这些抗体反应的结果从全身性B细胞失调。
Chronic humoral rejection (CHR) is a major complication after kidney transplantation. The cause of CHR is currently unknown. Autoantibodies have often been reported in kidney transplant recipients alongside anti-donor human leukocyte antigen antibodies. Yet, the lack of comprehensive studies has limited our understanding of this autoimmune component in the pathophysiology of CHR. By using a series of ELISA and immunocytochemistry assays, we assessed the development of autoantibodies in 25 kidney transplant recipients with CHR and 25 patients with stable graft function. We also compared the reactivity of five CHR and five non-CHR patient sera with 8027 recombinant human proteins using protein microarrays. We observed that a majority of CHR patients, but not non-CHR control patients, had developed antibody responses to one or several autoantigens at the time of rejection. Protein microarray assays revealed a burst of autoimmunity at the time of CHR. Remarkably, microarray analysis showed minimal overlap between profiles, indicating that each CHR patient had developed autoantibodies to a unique set of antigenic targets. The breadth of autoantibody responses, together with the absence of consensual targets, suggests that these antibody responses result from systemic B-cell deregulation.