Hoffmann Ute, Bergler Tobias, Segerer Stephan, Rümmele Petra, Krüger Bernd, Banas Miriam C, Reinhold Stephan, Banas Bernhard, Krämer Bernhard K
Department of Internal Medicine II-Nephrology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
Transpl Immunol. 2010 Aug;23(4):204-8. doi: 10.1016/j.trim.2010.06.006. Epub 2010 Jun 22.
Chemokine receptors play pivotal roles for leukocyte recruitment in acute and chronic inflammatory processes. This study was performed to analyze the expression, distribution and cellular localization of CX3CR1 in human renal transplant biopsies and to assess its role as potential diagnostic and prognostic marker. CX3CR1 was prospectively analyzed in 174 renal graft biopsies from patients with normal morphology (n=76), antibody-mediated acute rejection (n=6), acute tubulointerstitial rejection (n=27), acute vascular rejection (n=31), and with acute tubulus necrosis (n=34). Double immunofluorescence was additionally performed for CX3CR1 and CD4, CD8, CD20, CD68, and CD209/DC-SIGN. The number of CX3CR1 positive interstitial cells was significantly higher in the biopsies with acute tubulointerstitial and acute vascular rejection as compared to normal renal allograft biopsies. CX3CR1 positive cells were mainly CD68 positive monocytes/macrophages and CD209/DC-SIGN positive dendritic cells. The percentage of the CX3CR1 positive staining area was a predictor for steroid responsiveness and for worse clinical outcome 3 and 12 months after transplantation. CX3CR1 positive macrophages and/or dendritic cells are significantly elevated in acute renal allograft rejection. As CX3CR1 was associated with outcome parameters, it has to be further evaluated as a prognostic marker in human renal transplantation.
趋化因子受体在急性和慢性炎症过程中对白细胞募集起着关键作用。本研究旨在分析CX3CR1在人肾移植活检组织中的表达、分布及细胞定位,并评估其作为潜在诊断和预后标志物的作用。前瞻性分析了174例肾移植活检组织,这些患者的肾移植组织形态正常(n = 76)、存在抗体介导的急性排斥反应(n = 6)、急性肾小管间质排斥反应(n = 27)、急性血管排斥反应(n = 31)以及急性肾小管坏死(n = 34)。另外对CX3CR1与CD4、CD8、CD20、CD68和CD209/DC-SIGN进行了双重免疫荧光检测。与正常肾移植活检组织相比,急性肾小管间质和急性血管排斥反应的活检组织中CX3CR1阳性间质细胞数量显著更高。CX3CR1阳性细胞主要是CD68阳性的单核细胞/巨噬细胞和CD209/DC-SIGN阳性的树突状细胞。CX3CR1阳性染色区域的百分比可预测类固醇反应性以及移植后3个月和12个月时较差的临床结局。急性肾移植排斥反应中CX3CR1阳性巨噬细胞和/或树突状细胞显著增多。由于CX3CR1与结局参数相关,因此必须进一步评估其作为人肾移植预后标志物的价值。