Sis Banu, Grynoch Richard, Murray Allan G, Campbell Patricia, Solez Kim
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
Am J Kidney Dis. 2008 Jan;51(1):127-30. doi: 10.1053/j.ajkd.2007.08.023.
FTY720, a novel immunomodulator, causes rapid temporary depletion of peripheral-blood lymphocytes, inducing their sequestration in secondary lymphoid organs. FTY720 is effective in animal models of transplantation and is under evaluation for use in human transplantation. We report a 48-year-old renal transplant recipient who developed acute antibody-mediated rejection under a high-dose FTY720 (5 mg/d), low-dose cyclosporine A, and prednisone treatment protocol. A T-cell antihuman globulin and National Institutes of Health extended B-cell cross-match with donor cells were negative before transplantation. At 10 weeks posttransplantation, serum creatinine level increased and a renal biopsy showed a striking interstitial CD68(+) monocyte/macrophage infiltration with C4d staining of peritubular capillaries. Flow panel reactive antibody levels were positive in the recipient's serum for class I (9%) and class II (75%). The positive panel reactive antibody levels and presence of C4d in peritubular capillaries justified the diagnosis of antibody-mediated rejection. However, the presence of macrophage-rich interstitial infiltrate suggested a contribution of cellular rejection. The morphological characteristic of rejection with a striking interstitial CD68(+) monocyte/macrophage infiltration with paucity of T cells is very unusual and may reflect a unique effect of FTY720 therapy.
新型免疫调节剂FTY720可导致外周血淋巴细胞迅速短暂耗竭，促使其在二级淋巴器官中滞留。FTY720在移植动物模型中有效，目前正在评估其在人类移植中的应用。我们报告了一名48岁的肾移植受者，该患者在高剂量FTY720（5毫克/天）、低剂量环孢素A和泼尼松治疗方案下发生了急性抗体介导的排斥反应。移植前，T细胞抗人球蛋白和美国国立卫生研究院扩展的与供体细胞的B细胞交叉配型均为阴性。移植后10周，血清肌酐水平升高，肾活检显示间质有明显的CD68(+)单核细胞/巨噬细胞浸润，肾小管周围毛细血管C4d染色阳性。受者血清中I类（9%）和II类（75%）的流式细胞仪群体反应性抗体水平呈阳性。群体反应性抗体水平阳性以及肾小管周围毛细血管中存在C4d证实了抗体介导的排斥反应的诊断。然而，富含巨噬细胞的间质浸润提示存在细胞性排斥反应。排斥反应的形态学特征为间质有明显的CD68(+)单核细胞/巨噬细胞浸润且T细胞稀少，这种情况非常罕见，可能反映了FTY720治疗的独特作用。
