Reinke P, Fietze E, Döcke W D, Kern F, Ewert R, Volk H D
Department of Nephrology, Universitätsklinikum Charité, Humboldt-Universität, Berlin, Germany.
Transplantation. 1994 Jul 15;58(1):35-41.
Episodes of acute rejection can occur in functional renal grafts even at a very late stage after transplantation. They are not necessarily due to patient noncompliance. The incidence of late acute rejection is commonly underestimated because the diagnosis generally requires histopathology in order to rule out other origins of declining graft function, even more so, as the typical signs of acute rejection as seen in the early posttransplantation period (sudden and rapid increase of creatinine serum level, inflammatory signs) are missing. Histology revealed acute rejection in 157 of 412 renal allograft recipients suffering from progressive graft deterioration between the 2nd and 18th year after Tx. Late acute rejection was clearly associated with elevated levels of activated HLA-DR+ T cells in the peripheral blood. These cells were characterized by flow cytometry to be postmitotic activated effector-T cells belonging to the CD4+ and CD8+ "memory" T cell pool. The high sensitivity (97%) and specificity (88%) of flow cytometric analysis allows for the discrimination between late acute rejection and other causes of deteriorating graft function (infection, toxicity, arteriopathy, chronic rejection). Additionally, this immune monitoring can predict the success of antirejection therapy as early as a few days after initiation of treatment while conventional parameters do not reflect the therapeutic result until 1-3 weeks later. In addition to this, peripheral T cell activation also seems to identify a subgroup of patients with chronic rejection who would respond, at least partially, to steroid bolus therapy. As a result, this parameter is very useful for the clinical management of patients suffering from late deterioration of renal graft function.
即使在移植后非常晚的阶段，功能性肾移植中也可能发生急性排斥反应。它们不一定是由于患者不依从治疗所致。晚期急性排斥反应的发生率通常被低估，因为一般需要组织病理学检查来排除移植肾功能下降的其他原因，尤其是在移植后早期出现的急性排斥反应的典型体征（血清肌酐水平突然快速升高、炎症体征）不存在的情况下。组织学检查显示，在412例肾移植受者中，有157例在移植后第2年至第18年期间出现移植肾功能进行性恶化，存在急性排斥反应。晚期急性排斥反应与外周血中活化的HLA-DR+T细胞水平升高明显相关。通过流式细胞术对这些细胞进行鉴定，发现它们是属于CD4+和CD8+“记忆”T细胞池的有丝分裂后活化效应T细胞。流式细胞术分析具有高敏感性（97%）和特异性（88%），能够区分晚期急性排斥反应与移植肾功能恶化的其他原因（感染、毒性、动脉病变、慢性排斥反应）。此外，这种免疫监测能够在抗排斥治疗开始后几天就预测治疗的成功与否，而传统指标直到1 - 3周后才反映治疗结果。除此之外，外周血T细胞活化似乎还能识别出一部分慢性排斥反应患者，他们至少会对大剂量类固醇治疗有部分反应。因此，这个指标对于肾移植功能晚期恶化患者的临床管理非常有用。
