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胸腺球蛋白诱导治疗后肾移植中免疫细胞功能监测的意义

Significance of immune cell function monitoring in renal transplantation after Thymoglobulin induction therapy.

作者信息

Serban Geo, Whittaker Vaughn, Fan Jianshe, Liu Zhouru, Manga Kiran, Khan Muzammil, Kontogianni Katerina, Padmanabhan Anand, Cohen David, Suciu-Foca Nicole, Ratner Lloyd, Colovai Adriana I

机构信息

Department of Pathology, Columbia University, New York, New York, USA.

出版信息

Hum Immunol. 2009 Nov;70(11):882-90. doi: 10.1016/j.humimm.2009.07.027. Epub 2009 Aug 5.

Abstract

Monitoring of immune status in transplant recipients is essential for predicting the risk of rejection or infection. In this study, we assessed the significance of immune cell function in 76 renal allograft recipients after Thymoglobulin induction and initiation of maintenance immunosuppression. Using the Immuknow (Cylex Inc) assay, the amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin (PHA) was measured in patients whole blood. In parallel, the frequency and phenotype of CD4+ T cells were determined by flow cytometry. The Immuknow assay yielded paradoxically high ATP values during the first 3 months post-transplantation, despite very low CD4+ T cell counts. High ATP values were caused by peripheral blood myeloid cells, did not predict rejection, and occurred primarily in transplant recipients who received darbepoietin (p = 0.017). CD4+ T cells displayed predominantly an activated/memory phenotype and comprised a subpopulation of CD25+FOXP3+ cells. Over the first 5 months post-transplantation, mean ATP activity gradually decreased, whereas CD4+ T cell counts slowly increased. Low ATP values were predictive of infection (p = 0.002). Thus Immuknow results need to be interpreted with caution in patients receiving Thymoglobulin induction therapy. Although low ATP levels identify patients at increased risk for infection, high ATP values fail to correlate with rejection and do not justify increased immunosuppression.

摘要

监测移植受者的免疫状态对于预测排斥反应或感染风险至关重要。在本研究中,我们评估了76例接受胸腺球蛋白诱导及维持性免疫抑制治疗的肾移植受者免疫细胞功能的意义。使用Immuknow(Cylex公司)检测法,在患者全血中测量CD4+细胞对植物血凝素(PHA)反应产生的三磷酸腺苷(ATP)量。同时,通过流式细胞术确定CD4+ T细胞的频率和表型。尽管移植后前3个月CD4+ T细胞计数非常低,但Immuknow检测法却得出了反常的高ATP值。高ATP值是由外周血髓样细胞引起的,不能预测排斥反应,且主要发生在接受促红细胞生成素治疗的移植受者中(p = 0.017)。CD4+ T细胞主要表现为活化/记忆表型,并包含CD25+FOXP3+细胞亚群。在移植后的前5个月,平均ATP活性逐渐下降,而CD4+ T细胞计数则缓慢增加。低ATP值可预测感染(p = 0.002)。因此,在接受胸腺球蛋白诱导治疗的患者中,对Immuknow检测结果的解释需要谨慎。虽然低ATP水平可识别感染风险增加的患者,但高ATP值与排斥反应无关,也不能作为增加免疫抑制的依据。

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