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评估1型血管紧张素II受体和供体特异性抗内皮细胞抗体预测肾移植长期预后的潜力。

Assessing the potential of angiotensin II type 1 receptor and donor specific anti-endothelial cell antibodies to predict long-term kidney graft outcome.

作者信息

Pinelli David F, Friedewald John J, Haarberg Kelley M K, Radhakrishnan Shree L, Zitzner Jennifer R, Hanshew Wendy E, Tambur Anat R

机构信息

Northwestern University Feinberg School of Medicine, Comprehensive Transplant Center, Division of Transplant Surgery, 303 E Chicago Ave, Tarry Building Suite 11-763, Chicago, IL 60611, USA.

Northwestern University Feinberg School of Medicine, Comprehensive Transplant Center, Division of Transplant Surgery, 303 E Chicago Ave, Tarry Building Suite 11-763, Chicago, IL 60611, USA; Northwestern University, Division of Nephrology and Hypertension, Department of Medicine, 251 East Huron Street, Galter Suite 3-150, Chicago, IL 60611, USA.

出版信息

Hum Immunol. 2017 May-Jun;78(5-6):421-427. doi: 10.1016/j.humimm.2017.03.012. Epub 2017 Mar 31.

Abstract

Endothelial cell antigens have been reported as potential targets for antibodies in the context of organ transplantation, leading to increased risk for graft failure. Serum samples from 142 consecutive living donor kidney recipients were tested for the presence of antibodies to angiotensin II - type 1 receptor (AT1R), donor endothelial cells, and donor HLA. Graft survival was monitored for five years post-transplant, and secondary outcomes, including biopsy-proven rejection, proteinuria, biopsy-proven vasculopathy, and renal function based on serum creatinine were also assessed for the first two to three years. AT1R antibody levels were positive (>17U/mL) in 11.3%, 18.8% and 8.1% of patients pre-transplant, post-transplant and at time of indication biopsy, respectively. XM-ONE assay was positive in 17.6% of patients pre-transplant (7 IgG+; 15 IgM+; 3 IgG+/IgM+). Overall, 4 patients experienced antibody-mediated rejection (AMR), 31 borderline cellular rejection (BCR), 19 cellular rejection (CR) and 3 mixed AMR and CR within the first 24months. While pre-existing and de novo donor-specific HLA antibodies were associated with graft failure and many secondary outcomes, no statistical association was found for either anti-endothelial or anti-AT1R antibodies, indicating that these tests may not be the best predictors of graft outcome in living donor renal transplantation.

摘要

在内脏移植中,内皮细胞抗原已被报道为抗体的潜在靶点,这会增加移植失败的风险。对142例连续活体供肾受者的血清样本检测了抗血管紧张素II 1型受体(AT1R)、供体内皮细胞和供体HLA抗体的存在情况。移植后对移植物存活情况进行了5年监测,在前两到三年还评估了包括活检证实的排斥反应、蛋白尿、活检证实的血管病变以及基于血清肌酐的肾功能等次要结局。移植前、移植后和指示性活检时,AT1R抗体水平呈阳性(>17U/mL)的患者分别占11.3%、18.8%和8.1%。移植前17.6%的患者XM-ONE检测呈阳性(7例IgG阳性;15例IgM阳性;3例IgG和IgM均阳性)。总体而言,在最初24个月内,4例患者发生了抗体介导的排斥反应(AMR),31例发生了临界细胞排斥反应(BCR),19例发生了细胞排斥反应(CR),3例发生了混合性AMR和CR。虽然预先存在的和新发的供体特异性HLA抗体与移植失败及许多次要结局相关,但未发现抗内皮或抗AT1R抗体与这些有统计学关联,这表明在活体供肾移植中,这些检测可能并非移植物结局的最佳预测指标。

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