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监测肾移植受者CD4(+) T细胞内三磷酸腺苷以预测巨细胞病毒疾病的发生

Monitoring of intracellular adenosine triphosphate in CD4(+) T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients.

作者信息

Pérez-Jacoiste Asín María Asunción, Fernández-Ruiz Mario, López-Medrano Francisco, Aquilino Carolina, González Esther, Ruiz-Merlo Tamara, Gutiérrez Eduardo, San Juan Rafael, Paz-Artal Estela, Andrés Amado, Aguado José Maria

机构信息

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.

Department of Immunology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.

出版信息

Transpl Int. 2016 Oct;29(10):1094-105. doi: 10.1111/tri.12816. Epub 2016 Aug 1.

Abstract

The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P-value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.

摘要

测量植物血凝素刺激的CD4(+) T细胞中三磷酸腺苷(iATP)的细胞内浓度可作为移植后细胞介导免疫(CMI)的替代标志物。该检测方法在预测肾移植(KT)后感染方面的准确性欠佳。我们推测其预测能力取决于CMI对宿主-病原体相互作用的具体贡献。我们评估了100名KT受者在基线以及第1、3和6个月时的iATP水平(共363次测量)。尽管在巨细胞病毒(CMV)疾病方面这种关联很明显(多变量调整风险比[每增加50个单位]:0.83;P值 = 0.048),但未发现第1个月时的iATP与总体感染或细菌感染风险之间存在关联。在监测后的45天内,稳定患者(319.4 ng/ml)与发生总体感染(304.1 ng/ml)或细菌感染(346.9 ng/ml)的患者之间的平均iATP无显著差异。然而,发生CMV疾病的患者的iATP显著更低(223.5 ng/ml;P值<0.002)。对于未接受抗病毒预防的患者,预测CMV疾病的最佳临界值(265 ng/ml)的灵敏度、特异度、阳性预测值和阴性预测值分别为85.7%、68.3%、15.2%和98.6%。总之,通过iATP对CMI进行非病原体特异性监测可了解KT受者发生CMV疾病的风险。

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