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趋化因子配体 10 和 13 的表达在外周血单个核细胞中在急性排斥反应和抗排斥反应治疗反应不良时被高度上调。

CXCL10 and CXCL13 Expression were highly up-regulated in peripheral blood mononuclear cells in acute rejection and poor response to anti-rejection therapy.

机构信息

Kidney Disease Center, the First Affiliated Hospital of Medical College, Zhejiang University, 79 Qingchun road, Hangzhou, 310003, China.

出版信息

J Clin Immunol. 2011 Jun;31(3):414-8. doi: 10.1007/s10875-010-9500-8. Epub 2010 Dec 30.

Abstract

BACKGROUND

Acute rejection is still one of the main complications which enhances the cost and the risk to renal graft failure. Chemokines, interacting with respective receptors, can recruit leukocytes into grafts and mediate allograft rejection. In this study, we aimed to analyze gene expression of chemokines including CCL5/RANTES, CXCL10/IP-10, CXCL13/BCA-1, and receptors of CCR5, CXCR3, CXCR5 in peripheral blood mononuclear cells (PBMCs) during acute renal allograft rejection

METHODS

Gene expression of all these chemokines and receptors in PBMCs were analyzed by real-time PCR from 14 stable recipients, 32 biopsy-proven acute rejection (AR), and 5 acute tubular necrosis (ATN).

RESULTS

Gene expression of CCL5, CXCL10, CXCL13, and CCR5 were up-regulated both in AR and ATN group compared to stable recipients (fold change>2, P<0.05). Serum creatinine recovered to baseline level after anti-rejection therapy was defined as AR-sensitive and creatinine maintained above 200 μmol/L as AR-resistant. Expression of CXCL10 and CXCL13 were 5.98-, 2.94-, and 20.5, 10.8-fold change in AR-resistant and AR-sensitive compared to stable recipients, respectively. The expression of CXCL10 and CXCL13 was a twofold change in AR-resistant compared to AR-sensitive recipients (P<0.05). Five out of ten AR-resistant recipients lost graft function in the follow-up.

CONCLUSION

CXCL10 and CXCL13 expression were highly up-regulated in PBMCs in acute renal allograft rejection, especially in poor response to anti-rejection therapy and detrimental prognosis.

摘要

背景

急性排斥反应仍然是导致肾移植失败的成本和风险增加的主要并发症之一。趋化因子与相应的受体相互作用,可以募集白细胞进入移植物并介导同种异体移植排斥反应。在这项研究中,我们旨在分析包括 CCL5/RANTES、CXCL10/IP-10、CXCL13/BCA-1 在内的趋化因子以及 CCR5、CXCR3、CXCR5 受体在急性肾移植排斥反应期间外周血单个核细胞(PBMC)中的基因表达。

方法

通过实时 PCR 分析来自 14 例稳定受者、32 例活检证实的急性排斥反应(AR)和 5 例急性肾小管坏死(ATN)的所有这些趋化因子和受体的基因表达。

结果

与稳定受者相比,AR 和 ATN 组的 CCL5、CXCL10、CXCL13 和 CCR5 基因表达均上调(倍数变化>2,P<0.05)。抗排斥治疗后血清肌酐恢复至基线水平定义为 AR 敏感,肌酐维持在 200 μmol/L 以上定义为 AR 耐药。与稳定受者相比,AR 耐药和 AR 敏感患者 CXCL10 和 CXCL13 的表达分别为 5.98 倍、2.94 倍和 20.5 倍、10.8 倍。与 AR 敏感患者相比,AR 耐药患者 CXCL10 和 CXCL13 的表达增加了两倍(P<0.05)。在随访中,10 例 AR 耐药患者中有 5 例丧失了移植物功能。

结论

在急性肾移植排斥反应中,PBMC 中的 CXCL10 和 CXCL13 表达高度上调,尤其是对抗排斥治疗反应不良和预后不良的患者。

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