Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss
Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss
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DOI：
10.1111/ajt.12397
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发表时间：
2013-10-01
影响因子：
8.8
通讯作者：
Dragun, D.
中科院分区：
文献类型：
--
作者：
Giral, M.;Foucher, Y.;Dragun, D.
血管紧张素 II 1 型受体 (AT(1)R) 是功能性非 HLA 抗体 (Ab) 的新兴靶标。我们研究了确定 AT(1)R 预敏化程度作为移植物存活和急性排斥 (AR) 危险因素的潜力。该研究包括 1998 年至 2007 年间的 599 名肾脏接受者。使用定量固相测定法以盲法方式分析血清样本中的抗 AT(1)R 抗体 (AT(1)R-Abs)。 AT(1)R-Ab 水平的阈值根据移植失败时间统计确定为 10U。扩展的 Cox 模型确定了发生移植失败和第一次 AR 发作的危险因素。移植前 283 名患者 (47.2%) 检测到 AT(1)R-Abs >10U。 AT(1)R-Abs 水平 > 10U 的患者从移植后 3 年起移植失败的风险高出 2.6 倍 (p=0.0005)，并且在移植后的前 4 个月内发生 AR 发作的风险高出 1.9 倍 (p=0.0393)。抗体介导的排斥反应 (AMR) 占 AR 的 1/3，其中 71.4% 与 >10U 的移植前 AT(1)R-Ab 相关。移植前抗 AT(1)R-Ab 是长期移植物丢失的独立危险因素，与早期 AR 发作的较高风险相关。
The angiotensin II type 1 receptor (AT(1)R) is an emerging target of functional non-HLA antibodies (Ab). We examined the potential of determining the degree of presensitization against AT(1)R as a risk factor for graft survival and acute rejection (AR). The study included 599 kidney recipients between 1998 and 2007. Serum samples were analyzed in a blinded fashion for anti-AT(1)R antibodies (AT(1)R-Abs) using a quantitative solid-phase assay. A threshold of AT(1)R-Ab levels was statistically determined at 10U based on the time to graft failure. An extended Cox model determined risk factors for occurrence of graft failure and a first AR episode. AT(1)R-Abs >10U were detected in 283 patients (47.2%) before transplantation. Patients who had a level of AT(1)R-Abs >10U had a 2.6-fold higher risk of graft failure from 3 years posttransplantation onwards (p=0.0005) and a 1.9-fold higher risk of experiencing an AR episode within the first 4 months of transplantation (p=0.0393). Antibody-mediated rejection (AMR) accounted for 1/3 of AR, whereby 71.4% of them were associated with >10U of pretransplant AT(1)R-Abs. Pretransplant anti-AT(1)R-Abs are an independent risk factor for long-term graft loss in association with a higher risk of early AR episodes.