Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China.
Int Immunopharmacol. 2018 Feb;55:330-335. doi: 10.1016/j.intimp.2018.01.008. Epub 2018 Jan 6.
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.
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. sTim-3 was determined by ELISA. sGal-9 and sCEACAM-1 were determined by Bio-Plex® suspension array system.
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, SRL group showed significantly higher levels of sCEACAM-1 than TAC and HC groups.
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.
T 细胞免疫球蛋白黏蛋白-3（Tim-3）已被报道参与免疫反应的调节和同种异体移植物耐受的诱导。然而，Tim-3 与肾移植功能障碍之间的关系尚不清楚。我们研究了细胞和可溶性 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黏附分子-1（sCEACAM-1）在肾移植受者（KTR）中的表达，以探讨它们在移植物功能障碍中的作用。
纳入 96 例 KTR（53 例稳定移植物和 43 例移植物功能障碍）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 例受者进行了移植肾活检，14 例被诊断为活检证实的排斥反应（BPR）。通过流式细胞术测定细胞 Tim-3。通过 ELISA 测定 sTim-3。通过 Bio-Plex®悬浮阵列系统测定 sGal-9 和 sCEACAM-1。
与稳定受者相比，肾功能障碍的 KTR 显示出明显更高水平的 sTim-3 和 sGal-9，但细胞 Tim-3 和 sCEACAM-1水平相似。相关性分析显示，估算肾小球滤过率（eGFR）与 sTim-3 和 sGal-9 呈负相关。BPR 组和非 BPR 组的 Tim-3、Gal-9 和 CEACAM-1 水平相当。此外，SRL 组的 sCEACAM-1 水平明显高于 TAC 组和 HC 组。
sTim-3 和 sGal-9 是移植肾功能障碍的有前途的生物标志物，但不能区分移植肾排斥反应与 KTR 中其他原因引起的肾功能障碍。此外，与他克莫司相比，长期给予西罗莫司会增加 sCEACAM-1 水平，同时对 Tim-3 和 Gal-9 产生类似的调节作用。
