Department Internal Medicine, Section of Nephrology and Transplantation, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
Am J Transplant. 2017 Oct;17(10):2659-2667. doi: 10.1111/ajt.14280. Epub 2017 Apr 22.
Acute rejection is one of the major immunological determinants of kidney graft function and survival. Early biomarkers to predict rejection are lacking. Emerging evidence reveals a crucial role for the monocyte/macrophage lineage cells in the pathogenesis of rejection. We hypothesized that higher pretransplant numbers of proinflammatory CD16+ monocytes can predict rejection. The study cohort consisted of 104 kidney transplant recipients (58 with no rejection and 46 with biopsy-proven rejection) and 33 healthy persons. Posttransplant median follow-up time was 14.7 mo (interquartile range 0.3-34 mo). Pretransplantation blood samples were analyzed by flow cytometry for monocyte immunophenotypes. Groups were compared by Cox regression models for the occurrence of acute rejection. We documented a significantly increased absolute number of pretransplant CD16+ monocytes in patients who developed biopsy-proven rejection after transplantation compared with those with no rejection (hazard ratio [HR] 1.60, 95% CI 1.28-2.00, p < 0.001) and healthy persons (HR 1.47, 95% CI 1.18-1.82, p < 0.001). In parallel, significantly fewer absolute numbers of CD16- monocytes were observed at pretransplant time points in rejectors versus nonrejectors (HR 0.74, 95% CI 0.58-0.94, p < 0,014). A higher pretransplant number of CD16+ monocytes is significantly associated with a higher risk of acute rejection after kidney transplantation.
急性排斥反应是影响肾移植功能和存活的主要免疫学决定因素之一。目前缺乏预测排斥反应的早期生物标志物。新出现的证据表明,单核细胞/巨噬细胞谱系细胞在排斥反应的发病机制中起着至关重要的作用。我们假设移植前促炎 CD16+单核细胞数量较高可以预测排斥反应。该研究队列包括 104 例肾移植受者(58 例无排斥反应,46 例经活检证实的排斥反应)和 33 名健康人。移植后中位随访时间为 14.7 个月(四分位距 0.3-34 个月)。通过流式细胞术分析移植前血液样本中的单核细胞免疫表型。通过 Cox 回归模型比较各组急性排斥反应的发生情况。与无排斥反应的患者相比,发生经活检证实的排斥反应的患者移植前 CD16+单核细胞的绝对数量显著增加(危险比 [HR] 1.60,95%置信区间 1.28-2.00,p < 0.001)和健康人(HR 1.47,95%置信区间 1.18-1.82,p < 0.001)。同时,排斥组患者在移植前时间点的绝对 CD16-单核细胞数量明显减少(HR 0.74,95%置信区间 0.58-0.94,p < 0.014)。移植前 CD16+单核细胞数量较高与肾移植后急性排斥反应的风险增加显著相关。