Hosenpud J D, Everett J P, Morris T E, Mauck K A, Shipley G D, Wagner C R
Immunobiology Research Laboratory, Oregon Cardiac Transplant Program, Portland.
Circulation. 1995 Jul 15;92(2):205-11. doi: 10.1161/01.cir.92.2.205.
Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease responsible for the majority of late deaths after cardiac transplantation. Although most consider this complication a manifestation of chronic allograft rejection, it has not been established whether this disease is a consequence of humoral or cell-mediated alloreactivity.
Human aortic endothelial cells (HAECs) were isolated from donor aortas obtained at the time of organ acquisition for 52 cardiac allograft recipients. Serum and peripheral blood mononuclear cells were obtained from these 52 allograft recipients at several time points during the first year after transplantation. Lymphocyte proliferation (LP) in response to donor-specific HAECs and alloantibody binding to interferon-gamma-treated donor-specific HAECs were performed and correlated with clinical parameters, including HLA matching, acute cellular rejection, and coronary artery disease on surveillance angiography. Ten of the 52 patients studied had angiographic or autopsy evidence of coronary artery disease in the first posttransplantation year (CAV+ group). The CAV+ group had higher LP responses to their donor HAECs at 1 week, 3 months, and 6 months after transplantation compared with the CAV- group (1 week: 1439 +/- 222 versus 824 +/- 141 counts per minute [cpm], P = .026; 3 months: 1282 +/- 388 versus 884 +/- 94 cpm, P = .07; 6 months: 2504 +/- 635 versus 1540 +/- 209 cpm, P = .036; CAV+ versus CAV-, respectively). Only 8 of the 52 patients had donor-specific alloantibodies, and there was no relation between antibody presence and CAV. Other clinical parameters that correlated with CAV included the level of HLA-DR mismatch and the presence of late acute rejection.
CAV is associated with donor-specific cell-mediated alloreactivity to vascular endothelium. Humoral immunity does not appear to have a major role in this disease.
心脏移植血管病变（CAV）是一种加速型冠状动脉疾病，是心脏移植后大多数晚期死亡的原因。尽管大多数人认为这种并发症是慢性移植排斥反应的一种表现，但这种疾病是体液或细胞介导的同种异体反应性的结果尚未得到证实。
从52例心脏移植受者器官获取时的供体主动脉中分离出人主动脉内皮细胞（HAECs）。在移植后的第一年，从这52例移植受者的几个时间点获取血清和外周血单个核细胞。进行针对供体特异性HAECs的淋巴细胞增殖（LP）以及同种异体抗体与经干扰素-γ处理的供体特异性HAECs的结合，并与临床参数相关联，包括HLA配型、急性细胞排斥反应以及监测血管造影时的冠状动脉疾病。在研究的52例患者中，有10例在移植后的第一年有冠状动脉疾病的血管造影或尸检证据（CAV+组）。与CAV-组相比，CAV+组在移植后1周、3个月和6个月时对其供体HAECs的LP反应更高（1周：1439±222对824±141每分钟计数[cpm]，P = 0.026；3个月：1282±388对884±94 cpm，P = 0.07；6个月：2504±635对1540±209 cpm，P = 0.036；分别为CAV+与CAV-）。52例患者中只有8例有供体特异性同种异体抗体，抗体的存在与CAV之间没有关系。与CAV相关的其他临床参数包括HLA-DR错配水平和晚期急性排斥反应的存在。
CAV与针对血管内皮的供体特异性细胞介导的同种异体反应性相关。体液免疫在这种疾病中似乎没有主要作用。
