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Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier
| Title: | Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier |
| Authors: | Takada, Yusuke Browse this author | | Kamimura, Daisuke Browse this author →KAKEN DB | | Jiang, Jing-Jing Browse this author | | Higuchi, Haruka Browse this author | | Iwami, Daiki Browse this author →KAKEN DB | | Hotta, Kiyohiko Browse this author →KAKEN DB | | Tanaka, Yuki Browse this author →KAKEN DB | | Ota, Mitsutoshi Browse this author | | Higuchi, Madoka Browse this author | | Nishio, Saori Browse this author →KAKEN DB | | Atsumi, Tatsuya Browse this author →KAKEN DB | | Shinohara, Nobuo Browse this author →KAKEN DB | | Matsuno, Yoshihiro Browse this author →KAKEN DB | | Tsuji, Takahiro Browse this author →KAKEN DB | | Tanabe, Tatsu Browse this author | | Sasaki, Hajime Browse this author | | Iwahara, Naoya Browse this author | | Murakami, Masaaki Browse this author →KAKEN DB |
| Keywords: | chronic rejection | | cytokine | | chemokine | | tubular cells |
| Issue Date: | Oct-2020 |
| Publisher: | Oxford University Press |
| Journal Title: | International Immunology |
| Volume: | 32 |
| Issue: | 10 |
| Start Page: | 653 |
| End Page: | 662 |
| Publisher DOI: | 10.1093/intimm/dxaa032 |
| Abstract: | 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. |
| Rights: | This is a pre-copyedited, author-produced version of an article accepted for publication in International immunology following peer review. The version of record Yusuke Takada, Daisuke Kamimura, Jing-Jing Jiang, Haruka Higuchi, Daiki Iwami, Kiyohiko Hotta, Yuki Tanaka, Mitsutoshi Ota, Madoka Higuchi, Saori Nishio, Tatsuya Atsumi, Nobuo Shinohara, Yoshihiro Matsuno, Takahiro Tsuji, Tatsu Tanabe, Hajime Sasaki, Naoya Iwahara, Masaaki Murakami, Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier, International Immunology, Volume 32, Issue 10, October 2020, Pages 653-662, is available online at: https://doi.org/10.1093/intimm/dxaa032. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/82882 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 村上 正晃
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