Reinsmoen Nancy L, Mirocha James, Ensor Christopher R, Marrari Marilyn, Chaux George, Levine Deborah J, Zhang Xiaohai, Zeevi Adriana
1 HLA Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA. 2 Biostatistics Core, Research Institute and General Clinical Research Center and Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA. 3 School of Pharmacy, University of Pittsburgh Medical Center, Pittsburgh, PA. 4 Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, PA. 5 Pulmonary, Critical Care Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA. 6 University of Texas Health Science Center, San Antonio, TX. 7 Department of Immunology, University of Pittsburgh, Pittsburgh, PA.
Transplantation. 2017 Jun;101(6):1215-1221. doi: 10.1097/TP.0000000000001389.
The presence of antibodies to angiotensin type 1 receptor (AT1R) and endothelin type A receptor (ETAR) is associated with allograft rejection in kidney and heart transplantation. The aim of our study was to determine the impact of AT1R and ETAR antibodies on graft outcome in lung transplantation.
Pretransplant and posttransplant sera from 162 lung recipients transplanted at 3 centers between 2011 and 2013 were tested for antibodies to AT1R and ETAR by the enzyme-linked immunosorbent assay (ELISA) assay. Clinical parameters analyzed were: HLA antibodies at transplant, de novo donor-specific antibodies (DSA), antibody-mediated rejection (AMR), acute cellular rejection, and graft status.
Late AMR (median posttransplant day 323) was diagnosed in 5 of 36 recipients with de novo DSA. Freedom from AMR significantly decreased for those recipients with strong/intermediate binding antibodies to AT1R (P = 0.014) and ETAR (P = 0.005). Trends for lower freedom from acute cellular rejection were observed for recipients with pretransplant antibodies to AT1R (P = 0.19) and ETAR (P = 0.32), but did not reach statistical significance. Lower freedom from the development of de novo DSA was observed for recipients with antibodies detected pretransplant to AT1R (P = 0.054), ETAR (P = 0.012), and HLA-specific antibodies (P = 0.063). When the pretransplant antibody status of HLA-specific antibody (hazard ratio [HR], 1.69) was considered together with either strong binding to AT1R or ETAR, an increased negative impact on the freedom from the development of de novo DSA was observed (HR, 2.26 for HLA antibodies and ETAR; HR, 2.38 for HLA antibodies and ETAR).
These results illustrate the increased negative impact when antibodies to both HLA and non-HLA antigens are present pretransplant.
抗血管紧张素1型受体（AT1R）和内皮素A 型受体（ETAR）抗体的存在与肾移植和心脏移植中的移植物排斥反应相关。我们研究的目的是确定AT1R和ETAR抗体对肺移植中移植物结局的影响。
采用酶联免疫吸附测定（ELISA）法检测2011年至2013年间在3个中心接受肺移植的162例受者移植前和移植后的血清中AT1R和ETAR抗体。分析的临床参数包括：移植时的HLA抗体、新生供者特异性抗体（DSA）、抗体介导的排斥反应（AMR）、急性细胞排斥反应和移植物状态。
36例有新生DSA的受者中有5例被诊断为晚期AMR（移植后中位时间323天）。对于那些对AT1R（P = 0.014）和ETAR（P = 0.005）有强/中度结合抗体的受者，无AMR的概率显著降低。对于移植前有AT1R（P = 0.19）和ETAR（P = 0.32）抗体的受者，观察到急性细胞排斥反应的无发生率有降低趋势，但未达到统计学意义。对于移植前检测到有AT1R（P = 0.054）、ETAR（P = 0.012）和HLA特异性抗体（P = 0.063）的受者，新生DSA发生的无发生率较低。当将HLA特异性抗体的移植前抗体状态（风险比[HR]，1.69）与对AT1R或ETAR的强结合一起考虑时，观察到对新生DSA发生的无发生率有更大的负面影响（HLA抗体和ETAR的HR为2.26；HLA抗体和ETAR的HR为2.38）。
这些结果表明移植前同时存在HLA和非HLA抗原抗体时负面影响增加。
