Soluble Tim-3 and Gal-9 are associated with renal allograft dysfunction in kidney transplant recipients: A cross-sectional study
Soluble Tim-3 and Gal-9 are associated with renal allograft dysfunction in kidney transplant recipients: A cross-sectional study
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可溶性 Tim-3 和 Gal-9 与肾移植受者肾同种异体移植物功能障碍相关：一项横断面研究
DOI：
10.1016/j.intimp.2018.01.008
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发表时间：
2018-02-01
影响因子：
5.6
通讯作者：
Wang, Lan Lan
中科院分区：
文献类型：
--
作者：
Li, Ya Mei;Shi, Yun Ying;Wang, Lan Lan
背景资料：T细胞免疫球蛋白粘蛋白-3（Tim-3）参与免疫应答的调节和同种异体移植耐受的诱导。然而，Tim-3与肾移植功能障碍之间的关系尚不清楚。为探讨肾移植受者（KTRs）中细胞和可溶性Tim-3（sTim-3）、可溶性半乳糖凝集素-9（sGal-9）和癌胚抗原相关细胞粘附分子-1（sCEACAM-1）的表达在移植肾功能障碍中的作用，我们研究了96例KTRs（53例移植肾稳定，43例移植肾功能障碍）和30例健康对照（HC）。在KTR中，55例使用他克莫司（TAC），41例使用西罗莫司（SRL）。在功能障碍组中，29例接受移植物活检，14例被归类为活检证实的排斥反应（BPR）。流式细胞术测定细胞Tim-3。ELISA法测定slim-3。结果：肾功能不全的KTR与肾功能稳定的KTR相比，sTim-3和sGal-9的水平显著升高，而细胞Tim-3和sCEACAM-1的水平相似。相关分析显示，估计肾小球滤过率（eGFR）与sTim-3和sGal-9呈负相关。BPR和非BPR组均显示出相当水平的Tim-3、Gal-9和CEACAM-1。此外，SRI。结论：sTim-3和sGal-9可作为肾移植术后移植肾功能障碍的生物标志物，但不能鉴别肾移植排斥反应与其他原因引起的肾功能障碍。此外，长期给予西罗莫司可上调sCEACAM-1水平，而对Tim-3和Gal-9的调节作用与他克莫司相似。
Background: T cell immunoglobulin mucin-3 (Tim-3) has been reported to participate in the regulation of immune response and the induction of allograft tolerance. However, the association between Tim-3 and renal allograft dysfunction is unclear. We studied the expression of cellular and soluble Tim-3 (sTim-3), soluble galectin-9 (sGal-9) and carcinoembryonic antigen-related cell adhesion molecule-1 (sCEACAM-1) in kidney transplantation recipients (KTRs) to explore their roles in allograft dysfunction.Methods: 96 KTRs (53 with stable graft and 43 with graft dysfunction) and 30 healthy controls (HC) were enrolled. Among the KTRs, 55 used Tacrolimus (TAC) and 41 used Sirolimus (SRL). In the dysfunction group, 29 recipients have undergone graft biopsy and 14 were classified as biopsy-proven rejection (BPR). Cellular Tim-3 was determined by flow cytometry. slim-3 was determined by ELISA. sGal-9 and sCEACAM-1 were determined by Bio-Plex (R) suspension array system.Results: KTRs with renal dysfunction showed significantly higher levels of sTim-3 and sGal-9 but similar levels of cellular Tim-3 and sCEACAM-1 compared with stable recipients. Correlation analysis revealed that estimated glomerular filtration rate (eGFR) was negatively associated with sTim-3 and sGal-9. Both BPR and non-BPR groups showed comparable levels of Tim-3, Gal-9 and CEACAM-1. Moreover, SRI. group showed significantly higher levels of sCEACAM-1 than TAC and HC groups.Conclusions: sTim-3 and sGal-9 were promising biomarkers for allograft dysfunction, but unable to differentiate allograft rejection from other causes of renal dysfunction in KTRs. Moreover, long-term administration of sirolimus would up-regulate sCEACAM-1 level, while exert similar regulatory effects on Tim-3 and Gal-9 compared to tacrolimus.