Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier
Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier
复制标题
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
作者：
Takada;Y. Kamimura;D. Jiang;J;Higuchi;H. Iwami;D. Hotta;K. Tanaka;Y. Ota;M. Higuchi;M. Nishio;S. Atsumi;T. Shinohara;N. Matsuno;Y. Tsuji;T. Tanabe;T. Sasaki;H. Iwahara;N. Murakami;M.
慢性活性抗体介导的排斥反应（CAAMR）是肾移植（KTx）中的一个特殊问题，约25%的移植物因CAAMR而丢失。此外，发病机制仍不清楚，也没有有效的治疗方法或标志物。我们以前发现，在非免疫细胞中，一种称为IL-6放大器的超NFκ B激活机制是由NFκB和STAT 3的共激活诱导的，并且这种激活可以发展成各种慢性炎症性疾病。在这里，我们表明，突触结合蛋白-17（SYT 17）是增加的外泌体部分的尿液从CAAMR患者，这种增加是与激活的IL-6放大器。免疫组化显示CAAMR组肾小管细胞SYT 17蛋白表达增加。虽然通过蛋白质印迹法在全尿样中未检测到SYT 17蛋白，但与其他三个组织学组（正常、间质纤维化和肾小管萎缩和钙调磷酸酶抑制剂毒性）相比，CAAMR组中的尿外泌体SYT 17水平在KTx后显著升高。另一方面，目前的临床实验室数据无法区分CAAMR组与这些组。这些数据表明，尿外泌体SYT 17是CAAMR的潜在诊断标志物。
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.