Ulrich C, Heine G H, Gerhart M K, Köhler H, Girndt M
Department of Medicine IV, University of the Saarland, Homburg/Saar, Germany.
Am J Transplant. 2008 Jan;8(1):103-10. doi: 10.1111/j.1600-6143.2007.02035.x. Epub 2007 Nov 12.
Atherosclerotic cardiovascular disease is a major cause of death in renal transplant (TX) recipients. Atherosclerotic lesions are characterized by monocytic infiltration. Circulating monocytes can be divided into functionally distinct subpopulations, among which CD14++CD16+ and CD14+CD16+ monocytes (summarized as CD16+ monocytes) are proinflammatory cells. We hypothesized that the frequency of circulating CD16+ monocytes is associated with subclinical atherosclerosis in TX patients. Monocyte subpopulations were quantified in 95 TX and 31 hemodialysis patients (HD). In TX patients, subclinical atherosclerosis was determined by carotid intima media thickness (IMT) measurement. TX patients had lower frequencies of CD16+ monocytes than HD patients. When stratifying by immunosuppressive treatment, patients on methylprednisolone (MP) therapy had fewer CD14+CD16+ monocytes than patients not receiving MP. CD14+CD16+ monocytes decrease very shortly after transplantation. CD14+CD16+ monocyte frequency correlated with IMT in TX recipients (r = 0.34, p < 0.001). This correlation was most pronounced among patients without MP treatment (r = 0.55, p = 0.02). In a multivariate regression analysis, the association of CD14+CD16+ monocytes with IMT was independent from traditional cardiovascular risk factors. The frequency of proinflammatory CD14+CD16+ monocytes is independently associated with subclinical atherosclerosis in transplant recipients. Further studies on the association between circulating leukocytes and atherosclerosis should take monocyte heterogeneity into account.
动脉粥样硬化性心血管疾病是肾移植受者死亡的主要原因。动脉粥样硬化病变的特征是单核细胞浸润。循环单核细胞可分为功能不同的亚群,其中CD14++CD16+和CD14+CD16+单核细胞(统称为CD16+单核细胞)是促炎细胞。我们假设循环CD16+单核细胞的频率与肾移植患者的亚临床动脉粥样硬化有关。对95例肾移植患者和31例血液透析患者(HD)的单核细胞亚群进行了定量分析。在肾移植患者中,通过测量颈动脉内膜中层厚度(IMT)来确定亚临床动脉粥样硬化。肾移植患者的CD16+单核细胞频率低于血液透析患者。按免疫抑制治疗分层时,接受甲泼尼龙(MP)治疗的患者的CD14+CD16+单核细胞比未接受MP治疗的患者少。CD14+CD16+单核细胞在移植后很快减少。肾移植受者中CD14+CD16+单核细胞频率与IMT相关(r = 0.34,p < 0.001)。这种相关性在未接受MP治疗的患者中最为明显(r = 0.55,p = 0.02)。在多变量回归分析中,CD14+CD16+单核细胞与IMT的关联独立于传统心血管危险因素。促炎CD14+CD16+单核细胞的频率与移植受者的亚临床动脉粥样硬化独立相关。关于循环白细胞与动脉粥样硬化之间关联的进一步研究应考虑单核细胞的异质性。