IL‐6 production by monocytes is associated with graft function decline in patients with borderline changes suspicious for acute T‐cell‐mediated rejection: a pilot study
IL‐6 production by monocytes is associated with graft function decline in patients with borderline changes suspicious for acute T‐cell‐mediated rejection: a pilot study
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DOI：
10.1111/tri.13070
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发表时间：
2018-01
影响因子：
3.1
通讯作者：
O. Désy;S. Béland;P. Vallin;J. Riopel;É. Latulippe;N. Najafian;A. Chandraker;M. Agharazii;I. Batal;S. D. De Serres
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文献类型：
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作者：
O. Désy;S. Béland;P. Vallin;J. Riopel;É. Latulippe;N. Najafian;A. Chandraker;M. Agharazii;I. Batal;S. D. De Serres
尽管怀疑急性 T 细胞介导的排斥反应的边界变化 (BL) 代表了一个诊断类别，但其临床相关性受到质疑，导致治疗管理的异质性。我们假设通过测量外周血单核细胞的 IL-6 分泌来识别患有持续移植物损伤的患者。我们检查了分泌的 IL-6 与活检后 6 个月估计肾小球滤过率变化 (ΔeGFR) 之间的关联。然后，我们对患者和小鼠血液和肾脏中的先天免疫细胞进行了表型和功能研究。在训练集中，ΔeGFR 与 IL-6 水平密切相关，每增加 log10 IL-6，ΔeGFR 就会下降 4.6 ± 1.5 ml/min（P = 0.001），具有临床意义。这些结果在调整后是一致的，并且在验证队列中得到再现。外周血细胞表型分析显示IL-6的主要来源是CD14+CD16−CCR2+HLA-DR+CD86+CD11c+炎症单核细胞。活检中 IL-6 分泌与间质树突状细胞密度之间存在显着相关性。最后，小鼠肾脏树突状细胞的表征表明，它们与巨噬细胞具有相同的特征，并且具有分泌 IL-6 的效应细胞的功能。总之，测量外周血细胞分泌的 IL-6 可用于治疗没有并发炎症的 BL 患者。
Although borderline changes (BL) suspicious for acute T‐cell‐mediated rejection represent a diagnostic category, its clinical relevance is questioned leading to heterogeneous therapeutic management. We hypothesized that measuring IL‐6 secretion by peripheral blood mononuclear cells identifies patients with ongoing graft damage. We examined the association between secreted IL‐6 and the change in estimated glomerular filtration rate at 6 months after the biopsy (ΔeGFR). We then conducted phenotypic and functional studies on patient and mouse innate immune cells in the blood and the kidney. In a training set, ΔeGFR was strongly associated with IL‐6 levels, showing a clinically meaningful decline of 4.6 ± 1.5 ml/min per increase in log10 IL‐6 (P = 0.001). These results were consistent after adjustment and were reproduced in a validation cohort. Phenotyping of peripheral blood cells revealed that the main source of IL‐6 was CD14+CD16−CCR2+HLA‐DR+CD86+CD11c+ inflammatory monocytes. There was a significant correlation between IL‐6 secretion and interstitial dendritic cell density in the biopsy. Finally, characterization of mouse kidney dendritic cells revealed that they share features with macrophages and function as effector cells secreting IL‐6. In conclusion, measuring IL‐6 secreted by peripheral blood cells can be useful in the management of patients with BL in the absence of a concurrent inflammatory condition.