Woywodt Alexander, Schroeder Maik, Gwinner Wilfried, Mengel Michael, Jaeger Mark, Schwarz Anke, Haller Hermann, Haubitz Marion
Department of Medicine, Hannover Medical School, Hannover, Germany. woywodt.alexander@ mh-hannover.de.
Transplantation. 2003 Jul 15;76(1):1-4. doi: 10.1097/01.TP.0000074569.65127.26.
Damage of microvascular endothelial cells is a salient feature of acute vascular rejection and chronic allograft nephropathy, yet specific blood markers of ongoing endothelial injury are currently unavailable. Circulating endothelial cells have recently been established as a novel marker of endothelial damage in a variety of vascular disorders.
We studied 129 renal transplant recipients who underwent percutaneous graft biopsy. Circulating endothelial cells were isolated with immunomagnetic anti-CD146-coated Dynabeads. Cells were stained with acridine and counted. To verify their endothelial origin, staining for Ulex europaeus lectin 1 (UEA-1) was performed in parallel. Twenty-one healthy controls were also studied.
On biopsy, seven patients had acute vascular rejection, 15 patients had acute tubulointerstitial rejection, 14 patients had borderline rejection, and 93 patients had no rejection. Patients with acute vascular rejection had the highest cell numbers (72+/-39 cells/mL) when compared with all other patients (P<0.02). Regardless of their biopsy findings, however, all other renal transplant recipients had significantly higher numbers of circulating endothelial cells (25+/-20 cells/mL) than healthy controls (7+/-5 cells/mL, P<0.001). Finally, there was a significant correlation of cell numbers and serum cyclosporine A trough levels. By contrast, there was no correlation with serum creatinine, age, or the number of immunosuppressive drugs.
The number of circulating endothelial cells is a novel marker of endothelial damage in renal transplant recipients. Further studies must now evaluate the origin of these cells, corroborate the clinical significance of our findings, and delineate the influence of calcineurin inhibitors.
微血管内皮细胞损伤是急性血管排斥反应和慢性移植肾肾病的显著特征，但目前尚无正在发生的内皮损伤的特异性血液标志物。循环内皮细胞最近已被确立为多种血管疾病中内皮损伤的一种新型标志物。
我们研究了129例接受经皮移植肾活检的肾移植受者。用免疫磁珠抗CD146包被的Dynabeads分离循环内皮细胞。细胞用吖啶染色并计数。为了验证其内皮来源，同时进行欧洲荆豆凝集素1（UEA-1）染色。还研究了21名健康对照者。
活检时，7例患者发生急性血管排斥反应，15例患者发生急性肾小管间质排斥反应，14例患者发生临界排斥反应，93例患者无排斥反应。与所有其他患者相比，急性血管排斥反应患者的细胞数量最高（72±39个细胞/毫升）（P<0.02）。然而，无论活检结果如何，所有其他肾移植受者的循环内皮细胞数量（25±20个细胞/毫升）均显著高于健康对照者（7±5个细胞/毫升，P<0.001）。最后，细胞数量与血清环孢素A谷浓度之间存在显著相关性。相比之下，与血清肌酐、年龄或免疫抑制药物数量无关。
循环内皮细胞数量是肾移植受者内皮损伤的一种新型标志物。现在必须进行进一步研究，以评估这些细胞的来源，证实我们研究结果的临床意义，并阐明钙调神经磷酸酶抑制剂的影响。
