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Comprehensive examination of gene expression associated with long‐term stable graft acceptance by renal transplant recipients
Author(s) -
Zhang Huiqi,
Lu Hua,
Enosawa Shin,
Suzuki Seiichi,
Takahara Shiro,
Nakajima Toshiharu,
Saito Hirohisa,
Sakamoto Kaoru
Publication year - 2004
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2004.00118.x
Subject(s) - immunosuppression , medicine , immune system , gene , gene expression , kidney , peripheral blood mononuclear cell , immunology , transplantation , gene expression profiling , gene chip analysis , cd3 , microarray , cd8 , biology , genetics , in vitro
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.