Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients
Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients
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DOI：
10.1681/asn.2016070797
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发表时间：
2017-06-01
影响因子：
13.6
通讯作者：
Halloran, Philip F.
中科院分区：
文献类型：
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作者：
Aubert, Olivier;Loupy, Alexandre;Halloran, Philip F.
抗体介导的排斥反应（ABMR）可能发生在既存抗HLA供体特异性抗体（DSA）的患者或新发DSA的患者中。然而，这些过程如何比较同种异体移植物损伤和结果尚未得到解决。从来自两个北美和五个欧洲中心的771个肾活检标本的队列中，我们对所有ABMR患者（n=205）的临床和生物学参数、组织病理学、循环DSA和同种异体移植物基因表达进行了系统评估。总体而言，103例（50%）患者有既存DSA，102例（50%）患者有新发DSA。与既存DSA ABMR患者相比，新发DSA ABMR患者显示蛋白尿增加，移植肾小球病变更多，肾小球炎较低，但肾小管周围毛细血管炎和C4d沉积水平相似。与既存DSA ABMR相比，新生DSA ABMR的特征在于IFN γ诱导型、自然杀伤细胞和T细胞转录物的表达增加，但阿基转录物的表达减少。与初次DSA ABMR相比，预先存在的DSA ABMR具有上级的移植物存活率（排斥后8年分别为63%和34%; P
Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) had de novo DSA. Compared with patients with preexisting DSA ABMR, patients with de novo DSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition. De novo DSA ABMR was characterized by increased expression of IFN gamma-inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with the de novo DSA ABMR (63% versus 34% at 8 years after rejection, respectively; P