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题目:: Comparative Transcriptional and Phenotypic Peripheral Blood Analysis of Kidney Recipients under Cyclosporin A or Sirolimus Monotherapy
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状态:: 发布时间Oct. 1, 2010 , 更新时间 June 10, 2011 , 提交时间 June 7, 2010,
物种:: Homo sapiens
摘要:: Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4+CD25highFoxp3+ T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation. The complete database comprised the expression measurements of 54 675 genes for kidney trasplant recipient PBMC treated with SRL (n=23) and CSA (n=14) monotherapy. 9 healthy controls were also included.
实验种类:: transcription profiling by array
样本量:: 46
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数据号:: E-GEOD-22224, GSE22224
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