Comprehensive examination of gene expression associated with long‐term stable graft acceptance by renal transplant recipients
Comprehensive examination of gene expression associated with long‐term stable graft acceptance by renal transplant recipients
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DOI：
10.1111/j.1399-0012.2004.00118.x
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发表时间：
2004-02
影响因子：
2.1
通讯作者：
Hui-qi Zhang;Hua Lu;S. Enosawa;Seiichi Suzuki;S. Takahara;T. Nakajima;H. Saito;K. Sakamoto
中科院分区：
文献类型：
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作者：
Hui-qi Zhang;Hua Lu;S. Enosawa;Seiichi Suzuki;S. Takahara;T. Nakajima;H. Saito;K. Sakamoto
摘要：用GeneChips基因芯片仪器系统分析了5例肾移植受者和5例非移植对照外周血单个核细胞中mRNA的表达水平。所有受者在低剂量维持免疫抑制的情况下，移植肾功能正常的时间均超过15年。在12630个转录本中，观察到599个基因的显著差异表达，其中470个基因在移植受者中上调，129个基因在对照组中下调。其中192个表达上调的基因和46个表达下调的基因变化超过2倍，被分为8个功能类别：免疫系统(12/14)、细胞增殖(17/3)、肿瘤(15/3)、转运蛋白/受体/结合蛋白(16/5)、转录因子(8/2)、酶(17/4)、表达序列标签(91/9)和其他(16/6)。不出所料，受者体内免疫相关基因的表达减少。CD3、ICAM-1和B7.2的表达水平显著降低，CD3、ICAM-1和B7.2是抗原提呈细胞和T细胞相互作用的关键分子。在T细胞信号转导中，RAS通路可能被HVH-5激活所抑制。本研究结果有助于阐明长期肾移植受者的免疫学状态，并可能为未来建立供者特异性低反应性的方案提供启示。
Abstract: Expression levels of mRNA in peripheral blood mononuclear cells from five renal transplant recipients and five non‐transplanted controls were analyzed with GeneChips (GeneChip Instrument system, Affymetrix, Santa Clara, CA, USA). All recipients had retained a well‐functioning kidney graft for more than 15 yr on low‐dose maintenance immunosuppression. Among a total of 12 630 transcripts examined, significant differential expression was observed for 599 genes, whereby 470 genes were up‐regulated and 129 down‐regulated in the transplant recipients compared with controls. Of these, 192 up‐regulated and 46 down‐regulated genes showing a change greater than twofold were divided into eight functional categories as follows (numbers of genes, up/down): immune system (12/14), cell proliferation (17/3), oncology (15/3), transporter/receptor/binding protein (16/5), transcription factors (8/2), enzymes (17/4), expressed sequence tags (91/9), and others (16/6). Predictably, expression of immune‐associated genes was decreased in the recipients. Significant reduction of expression levels of CD3, ICAM‐1, and B7.2, which are critical molecules for interactions between antigen presenting cells and T cells, were observed. In T cell signal transduction, the Ras pathway was likely to be suppressed by activation of hVH‐5. The present data help to elucidate the immunological status in long‐term kidney graft recipients and may provide insights for future regimens to establish donor‐specific hyporesponsiveness.