Philogene Mary Carmelle, Zhou Sheng, Lonze Bonnie E, Bagnasco Serena, Alasfar Sami, Montgomery Robert A, Kraus Edward, Jackson Annette M, Leffell Mary S, Zachary Andrea A
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, United States.
Hum Immunol. 2018 Apr;79(4):195-202. doi: 10.1016/j.humimm.2018.02.001. Epub 2018 Feb 8.
Retrospective studies of angiotensin II type 1 receptor antibodies (AT1R-Ab) and anti-endothelial cell antibodies (AECA) have linked these antibodies to allograft injury. Because rising healthcare costs dictate judicious use of laboratory testing, we sought to define characteristics of kidney transplant recipients who may benefit from screening for non-HLA antibodies. Kidney recipients transplanted between 2011 and 2016 at Johns Hopkins, were evaluated for AT1R-Ab and AECA. Pre-transplant antibody levels were compared to clinical and biopsy indications of graft dysfunction. Biopsies were graded using the Banff' 2009-2013 criteria. AT1R-Ab and AECA were detected using ELISA and endothelial cell crossmatches, respectively. AT1R-Ab levels were higher in patients who were positive for AECAs. Re-transplanted patients (p < 0.0001), males (p = 0.008) and those with FSGS (p = 0.04) and younger (p = 0.04) at time of transplantation were more likely to be positive for AT1R-Ab prior to transplantation. Recipients who were positive for AT1R-Ab prior to transplantation had increases in serum creatinine within 3 months post-transplantation (p < 0.0001) and developed abnormal biopsies earlier than did AT1R-Ab negative patients (126 days versus 368 days respectively; p = 0.02). Defining a clinical protocol to identify and preemptively treat patients at risk for acute rejection with detectable non-HLA antibodies is an important objective for the transplant community.
对1型血管紧张素II受体抗体（AT1R-Ab）和抗内皮细胞抗体（AECA）的回顾性研究已将这些抗体与同种异体移植损伤联系起来。由于不断上涨的医疗成本要求合理使用实验室检测，我们试图确定可能受益于非HLA抗体筛查的肾移植受者的特征。对2011年至2016年在约翰霍普金斯医院接受移植的肾移植受者进行了AT1R-Ab和AECA评估。将移植前抗体水平与移植物功能障碍的临床和活检指标进行比较。活检采用2009 - 2013年班夫标准进行分级。分别使用酶联免疫吸附测定（ELISA）和内皮细胞交叉配型检测AT1R-Ab和AECA。AECA呈阳性的患者中AT1R-Ab水平更高。再次移植的患者（p＜0.0001）、男性（p = 0.008）、移植时患有局灶节段性肾小球硬化（FSGS）的患者（p = 0.04）以及较年轻的患者（p = 0.04）在移植前更有可能AT1R-Ab呈阳性。移植前AT1R-Ab呈阳性的受者在移植后3个月内血清肌酐升高（p＜0.0001），并且比AT1R-Ab阴性患者更早出现活检异常（分别为126天和368天；p = 0.02）。制定一个临床方案来识别和预先治疗有可检测到的非HLA抗体的急性排斥风险患者是移植界的一个重要目标。
