Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation (KTx), and ~25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this activation can develop various chronic inflammatory diseases. Here, we show that synaptotagmin-17 (SYT17) is increased in an exosomal fraction of the urine from CAAMR patients, and that this increase is associated with activation of the IL-6 amplifier. Immunohistochemistry showed that SYT17 protein expression was increased in renal tubule cells of the CAAMR group. While SYT17 protein was not detectable in whole-urine samples by western blotting, urinary exosomal SYT17 levels were significantly elevated in the CAAMR group compared to three other histology groups (normal, interstitial fibrosis and tubular atrophy, and calcineurin inhibitors toxicity) after KTx. On the other hand, current clinical laboratory data could not differentiate the CAAMR group from these groups. These data suggest that urinary exosomal SYT17 is a potential diagnostic marker for CAAMR.

中文翻译：

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通过 IL-6 放大器在肾移植后慢性活性抗体介导的排斥反应中尿外泌体 SYT17 水平增加。

慢性活性抗体介导的排斥 (CAAMR) 是肾移植 (KTx) 中的一个特殊问题，CAAMR 会丢失约 25% 的移植物。此外，发病机制尚不清楚，也没有有效的治疗方法或标志物。我们之前发现，非免疫细胞中称为 IL-6 放大器的超 NFκB 激活机制是由 NFκB 和 STAT3 的共激活诱导的，并且这种激活可以发展为各种慢性炎症性疾病。在这里，我们表明突触结合蛋白 17 (SYT17) 在来自 CAAMR 患者的尿液的外泌体部分中增加，并且这种增加与 IL-6 放大器的激活有关。免疫组化显示CAAMR组肾小管细胞中SYT17蛋白表达增加。虽然通过蛋白质印迹法在全尿液样本中检测不到 SYT17 蛋白，在 KTx 后，与其他三个组织学组（正常、间质纤维化和肾小管萎缩以及钙调磷酸酶抑制剂毒性）相比，CAAMR 组的尿外泌体 SYT17 水平显着升高。另一方面，目前的临床实验室数据无法将 CAAMR 组与这些组区分开来。这些数据表明，尿液外泌体 SYT17 是 CAAMR 的潜在诊断标志物。