BACKGROUND Infections remain the second most common cause of death in patients with end-stage kidney disease (ESKD). We aimed to evaluate non-specific cell-mediated immunity in an ESKD cohort using a functional assay applicable to routine use, QuantiFERON-Monitor (Qiagen), and assess whether it can predict infectious events. METHODS In this prospective study, we performed the QuantiFERON-Monitor test in 80 subjects including 54 patients with ESKD. QuantiFERON-Monitor is based on the measurement of plasma interferon-gamma (IFN-γ) after stimulation of NK-cells with a TLR-7 agonist, and T-cells with a TCR agonist. Patients were subsequently followed for 6 to 12 months. RESULTS QuantiFERON-Monitor showed lower stimulated IFN-γ production in ESKD patients (n = 54) compared to healthy donors (n = 19) (p < 0.0001) and to chronic kidney disease stage 3-4 patients (n = 7) (hemodialysis (n = 30): p < 0.01; peritoneal dialysis (n = 13): p = 0.03 and ESKD on conservative management (n = 11): p < 0.001). No significant difference in stimulated IFN-γ production was observed between ESKD patients with renal replacement therapies or conservative management. Stimulated IFN-γ production was significantly lower in patients later developing infections (13.9 [5.5-48.3] IU/mL vs 85.8 [35.5-236] IU/mL, p = 0.007). Using ROC analysis, we identified a cutoff value of 63.55 IU/mL (sensitivity = 80.95%, specificity = 79.17%, AUC = 0.78, p = 0.008) to discriminate patients at higher risk of infections. Patients with stimulated IFN-γ levels measured by QuantiFERON Monitor below 63.55 IU/mL (n = 21) had a hazard ratio of 10.71 ([3.68-31.13], p < 0.0001) for the development of subsequent infections. CONCLUSION Monitoring of IFN-γ production after stimulation of innate and adaptive immunity may identify ESKD patients with high risk of infection. This allows for therapeutic interventions to restore cellular immunity, thereby minimizing both infections and rejections after kidney-transplantation.

中文翻译：

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使用干扰素-γ的功能性免疫分析可以预测终末期肾脏疾病的感染事件。

背景技术感染仍是终末期肾脏病（ESKD）患者的第二大常见死亡原因。我们旨在使用适用于常规用途的功能测定QuantiFERON-Monitor（Qiagen）评估ESKD队列中的非特异性细胞介导的免疫，并评估其是否可以预测感染事件。方法在这项前瞻性研究中，我们对80名受试者（包括54名ESKD患者）进行了QuantiFERON-Monitor测试。QuantiFERON-Monitor基于对TLR-7激动剂刺激NK细胞和TCR激动剂刺激T细胞后血浆干扰素-γ（IFN-γ）的测量。随后对患者进行了6到12个月的随访。结果QuantiFERON-Monitor显示ESKD患者（n = 54）的刺激的IFN-γ产生低于健康供体（n = 19）（p <0。0001）和3-4例慢性肾脏疾病患者（n = 7）（血液透析（n = 30）：p <0.01;腹膜透析（n = 13）：p = 0.03和保守治疗的ESKD（n = 11） ：p ＜0.001）。在有肾脏替代疗法或保守治疗的ESKD患者之间，未观察到刺激的IFN-γ产生的显着差异。在后来发展成感染的患者中，刺激的IFN-γ产生显着降低（13.9 [5.5-48.3] IU / mL与85.8 [35.5-236] IU / mL，p = 0.007）。使用ROC分析，我们确定了63.55 IU / mL的临界值（敏感性= 80.95％，特异性= 79.17％，AUC = 0.78，p = 0.008），以区分感染风险较高的患者。通过QuantiFERON Monitor测得的刺激的IFN-γ水平低于63.55 IU / mL（n = 21）的患者的危险比为10.71（[3.68-31.13]，p <0。0001）用于后续感染的发展。结论监测先天性和适应性免疫后对IFN-γ产生的监测可确定ESKD患者具有高感染风险。这允许进行治疗性干预以恢复细胞免疫力，从而将肾脏移植后的感染和排斥反应降至最低。