Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.
Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.
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DOI：
10.1371/journal.pone.0156900
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Banas B
中科院分区：
文献类型：
--
作者：
Bergler T;Jung B;Bourier F;Kühne L;Banas MC;Rümmele P;Wurm S;Banas B
尽管近年来取得了实质性进展，但移植物存活超过第一年仍需要改进。由于现代免疫抑制主要针对T细胞活化和增殖，我们研究了103例肾移植受者在急性抗体和T细胞介导的排斥反应期间巨噬细胞浸润到同种异体移植物中。巨噬细胞浸润与移植物功能和移植物存活相关，直至移植后36个月。在抗体介导和T细胞介导的排斥反应中，巨噬细胞浸润显著升高，但在已建立IFTA的肾脏中没有。对于同种异体移植物中巨噬细胞浸润较明显的患者，类固醇治疗排斥反应的成功率较低。巨噬细胞浸润伴随着细胞增殖和抗原呈递的增加。在房室分布方面，T细胞介导的排斥反应的严重程度与CD68+细胞的数量相关，特别是在管周和血管周室，而ABMR活检显示主要是管周CD68浸润。此外，如多变量分析所示，巨噬细胞浸润的严重程度是肾移植后两周以及两年和三年的肌酐值的有效预测因子。此外，进行的ROC曲线分析显示，巨噬细胞浸润的程度（低于与高于中位数）是重新开始透析必要性的有效预测因子。根据巨噬细胞浸润的程度进行额外的分层活检，不同的CD68+细胞浸润反映在整体移植物存活率的显著差异上。急性同种异体移植物排斥反应的差异不仅反映在不同程度的巨噬细胞浸润，而且还反映在隔室特异性浸润模式和随后对同种异体移植物功能的影响以及对透析启动的需要。巨噬细胞浸润、伴随的抗原呈递和导致的同种异体移植物功能之间存在强有力的关系。
Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation. Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median) was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival. The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis initiation. There is a robust relationship between macrophage infiltration, accompanying antigen-presentation and resulting allograft function.