Cytotoxic lymphocyte gene expression in peripheral blood leukocytes correlates with rejecting renal allografts

Cytotoxic lymphocyte gene expression in peripheral blood leukocytes correlates with rejecting renal allografts
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DOI:
10.1097/00007890-199809150-00002
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发表时间:
1998-09-15
期刊:
影响因子:
6.2
通讯作者:
Strom, TB
Strom, TB
中科院分区:
医学2区
文献类型:
--
作者:
Vasconcellos, LM;Asher, F;Strom, TB

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背景我们先前已经表明细胞毒性淋巴细胞(CL)效应基因穿孔素(P)、颗粒酶B(GB)和Fas配体(FasL)的表达升高与急性同种异体移植物排斥密切相关,特别是当两个或更多个靶基因上调时。我们采用定量逆转录-聚合酶链反应分析CL基因表达从外周血白细胞(PBL)和肾移植活检在31对样本的PBL和肾组织从25个肾移植受者。我们的目的是(1)确定PBL中CL基因表达是否与这些基因在肾移植活检组织中的表达相关;(2)确定PBL中CL基因表达是否与组织学诊断相关。在P组9/11例(82%)、GB组07/11例(64%)和Fast组10/11例(91%)中发现PBL和急性排斥同种异体移植物中的协调基因表达。在非排斥性同种异体移植物中,P组15/20(75%)、GB组17/20(85%)和Fast组16/20(80%)出现协调缺失。PBL中任意两个基因的上调与排斥反应的病理诊断相关,阳性预测值为100%,阴性预测值为95%。在外周血淋巴细胞和同种异体移植物中,CL基因的协调表达通常被检测到。CL基因表达与排斥反应的病理诊断密切相关。外周血淋巴细胞CL基因表达可作为监测肾移植排斥反应的一种无创性方法。
Background. We have shown previously that heightened expression of the cytotoxic lymphocyte (CL) effector genes perforin (P), granzyme B (GB), and Fas ligand (FasL), is closely correlated with acute allograft rejection, particularly when two or more target genes are up-regulated.Methods. We used quantitative reverse transcription-polymerase chain reaction to analyze CL gene expression from peripheral blood leukocytes (PBLs) and renal allograft biopsies in 31 paired samples of PBLs and renal tissue from 25 renal allograft recipients. Our aims were (1) to determine whether the expression of CL gene expression in PBLs correlates with expression of these genes in renal allograft biopsy tissue and (2) to determine whether CL gene expression in PBLs correlates with the histological diagnosis,Results. Coordinate gene expression in PBLs and acutely rejecting allografts was found in 9/11 (82%) for P, 07/11 (64%) for GB, and 10/11 (91%) for Fast. Coordinate absence was found in 15/20 (75%) for P, 17/20 (85%) for GB, and 16/20 (80%) for Fast in nonrejecting allografts. Furthermore, up-regulation of any two genes in PBLs correlated with pathological diagnosis of rejection with excellent positive (100%) and negative (95%) predictive values.Conclusion. Coordinate CL gene expression in PBLs and the allograft is usually detected. CL gene expression in PBLs is closely associated with a pathologic diagnosis of rejection. CL gene expression in PBLs may serve as a noninvasive method of monitoring for renal allograft rejection.