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人类白细胞抗原G及其抑制性受体监测在肾移植术后的应用

[Applications of monitoring human leukocyte antigen G and its inhibitory receptors in post-renal transplantation].

作者信息

XIAO Li, SHI Bing-yi, GAO Yu, CAI Ming, Qian Ye-yong, HE Xiu-yun, XU Xiao-guang, HAN Yong, ZHOU Wen-qiang, MENG Xiao-yun, HAN Meng-xia

机构信息

Basic Research Lab, Organ Transplant Center, No. 309 Hospital of PLA, Beijing 100091, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2010 Sep 28;90(36):2524-7.

PMID:21092455
Abstract

OBJECTIVE

to study the feasibility of human leucocyte antigen-G (HLA-G) as a post-transplantation prognostic biomarker and discuss the correlation of its receptor expression and the mechanisms.

METHODS

a total of 215 recipients in our centre from February 2006 to June 2008 were divided into stable kidney function group (n = 173) and acute rejection group (n = 42). The soluble human leucocyte antigen-G5 (sHLA-G5) level in peripheral plasma was detected by ELISA. And the HLA-G receptor ILT-2, KIR2DL4 on T, B, NK lymphocytes were analyzed by flow cytometry (FCM). The sHLA-G5 cutoff level by ROC curve was employed to predict the events of acute post-transplantation rejection. And regression analysis was used to determine the association of sHLA-G5 with acute rejection.

RESULTS

an optimal cutoff value of 139.0 microg/L could be defined for sHLA-G5 (sensitivity: 63.6%, specificity: 82.1%, AUC: 0.780). Binary regression analysis showed that sHLA-G5 played an independent role on acute rejection (P = 0.019, OR = 0.039, 95%CI: 2.091 - 5.661). The rate of HLA-G receptor ILT-2 on CD4(+)T cell, CD8(+)T cell and B cell in acute rejection group was statistically lower than that in stable kidney function group (21% ± 7% vs 52% ± 17%, 23% ± 6% vs 39% ± 16%, 21% ± 7% vs 39% ± 16%, all P < 0.05). The expression of KIR2DL4 on NK cells in acute rejection group was statistically lower than that in stable kidney function group (31% ± 10%vs 57% ± 21%, P < 0.05).

CONCLUSION

sHLA-G5 level may be predicted for acute rejection with a high sensitivity and specificity. The up-regulated expression of ILT-2 and KIR2DLT may contribute to immunology tolerance in peripheral circulation.

摘要

目的

研究人类白细胞抗原-G(HLA-G)作为移植后预后生物标志物的可行性,并探讨其受体表达的相关性及机制。

方法

选取2006年2月至2008年6月在本中心的215例受者,分为肾功能稳定组(n = 173)和急性排斥组(n = 42)。采用酶联免疫吸附测定法(ELISA)检测外周血浆中可溶性人类白细胞抗原-G5(sHLA-G5)水平。通过流式细胞术(FCM)分析T、B、NK淋巴细胞上的HLA-G受体ILT-2、KIR2DL4。采用ROC曲线确定的sHLA-G5临界值预测移植后急性排斥事件。采用回归分析确定sHLA-G5与急性排斥的相关性。

结果

sHLA-G5的最佳临界值为139.0μg/L(灵敏度:63.6%,特异性:82.1%,AUC:0.780)。二元回归分析显示sHLA-G5在急性排斥中起独立作用(P = 0.019,OR = 0.039,95%CI:2.091 - 5.661)。急性排斥组中CD4(+)T细胞、CD8(+)T细胞和B细胞上HLA-G受体ILT-2的比例低于肾功能稳定组(21%±7%对52%±17%,23%±6%对39%±16%,21%±7%对39%±16%,均P < 0.05)。急性排斥组NK细胞上KIR2DL4的表达低于肾功能稳定组(31%±10%对57%±21%,P < 0.05)。

结论

sHLA-G5水平可用于预测急性排斥,具有较高的灵敏度和特异性。ILT-2和KIR2DLT表达上调可能有助于外周循环中的免疫耐受。

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Zhonghua Yi Xue Za Zhi. 2010 Sep 28;90(36):2524-7.
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