Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients
Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients
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DOI：
10.1093/rheumatology/kei244
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发表时间：
2006-06-01
期刊：
影响因子：
5.5
通讯作者：
Arnett, FC
中科院分区：
文献类型：
--
作者：
Tan, FK;Zhou, X;Arnett, FC
Objective.通过外周血细胞（PBCs）的转录谱分析，全面了解早期系统性硬化症（SSc）的免疫学改变。使用寡核苷酸微阵列比较18例SSc病例（病程< 2年）和18例对照者的PBC基因表达谱，这些病例在种族、性别和种族上相匹配。SSc病例既往或当前未暴露于细胞毒性药物。PAXgene管用于在静脉切开术期间稳定RNA。基因表达的变化通过实时聚合酶链反应进行独立验证。SSc PBMC表现出18个干扰素诱导基因的差异表达。这些基因中的六个与狼疮外周血单核细胞中的干扰素标记基因相同。值得注意的是，SSc PBMC还具有增加的同种异体移植物炎性因子（AIF1）和参与细胞粘附至内皮的几种选择素和整合素的表达。对284条已知的生物学通路的分析显示，SSc PBMC中有13条通路受到差异调节，其中包括两条导致T（H）2极化的通路（IL 2RB和GATA 3）。转录谱可靠地区分来自SSc和正常供体的PBMC，尽管它们代表异质性细胞群体。多种生物学途径在SSc PBMC中差异调节，但这些途径的共同点是蛋白酪氨酸激酶2 β和促分裂原活化蛋白激酶信号传导的改变。尽管SSc PBC基因表达谱与狼疮干扰素基因特征表现出一些相似之处，但编码将PBMC靶向内皮的蛋白质的转录物的表达也增加，这可能与SSc的血管病变相关。
Objective. To obtain a global view of the immunological alterations occurring in early systemic sclerosis (SSc) by transcriptional profiling of peripheral blood cells (PBCs).Methods. Otigonucleotide microarrays were used to compare PBC gene expression profiles in 18 SSc cases (< 2 yr duration) and 18 controls matched for race, gender and ethnicity. SSc cases had no prior or current exposure to cytotoxic drugs. PAXgene tubes were used to stabilize RNA during phlebotomy. Changes in gene expression were independently validated by real-time polymerase chain reaction.Results. SSc PBCs demonstrated differential expression of 18 interferon-inducible genes. Six of these genes were identical to the interferon signature genes in lupus peripheral blood mononuclear cells. Notably, SSc PBCs also had increased expression of allograft inflammatory factor (AIF1) and several selectins and integrins involved in cellular adhesion to the endothelium. Global analysis of 284 known biological pathways revealed that 13 were differentially regulated in SSc PBCs, including two pathways (IL2RB and GATA3) that lead to T(H)2 polarization.Conclusions. Transcriptional profiling reliably discriminates between PBCs from SSc and normal donors despite the fact that they represent a heterogeneous cell population. Multiple biological pathways were differentially regulated in SSc PBCs, but a common thread across these pathways was alterations in protein tyrosine kinase 2 beta and mitogen-activated protein kinase signalling. Although the SSc PBC gene expression profile demonstrated some parallels with the lupus interferon gene signature, there was also increased expression of transcripts encoding proteins that target PBCs to the endothelium, which might be relevant to the vasculopathy of SSc.