Coordinate overexpression of interferon-α-induced genes in systemic lupus erythematosus
Coordinate overexpression of interferon-α-induced genes in systemic lupus erythematosus
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DOI：
10.1002/art.20798
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Crow, MK
中科院分区：
文献类型：
--
作者：
Kirou, KA;Lee, C;Crow, MK
客观的。研究干扰素-α (IFNα) 和 IFNgamma 对 IFN 基因表达特征的贡献，该特征在系统性红斑狼疮 (SLE) 患者外周血单核细胞 (PBMC) 的微阵列筛查中观察到。方法。使用健康对照 PBMC 的定量实时聚合酶链反应分析来确定 IFNα 和 IFNgamma 对一组 IFN 诱导基因 (IFIG) 的相对诱导。将 77 名 SLE 患者的 PBMC 与 22 名疾病对照者和 28 名健康供体的 PBMC 的 IFIG 表达进行了比较。结果。 SLE PBMC 中 IFNα 诱导基因的表达显着高于疾病对照或健康供体的 PBMC。 IFNα 通路激活的 SLE 患者的 PBMC 中所有 IFIG 的表达水平与这些基因对 IFNα 的固有反应性高度相关，表明该细胞因子通路的协调激活。与对照 PBMC 相比，SLE PBMC 中 IFNγ 优先诱导的基因表达没有显着增加。在一些 SLE 血浆样本中检测到 IFNα 调节的基因诱导活性。结论。 IFNα 诱导基因的协调激活是许多 SLE 患者 PBMC 的一个特征，这支持了 IFNa 是狼疮中 IFIG 表达的主要刺激物的假设。
Objective. To study the contribution of interferon-alpha (IFNalpha) and IFNgamma to the IFN gene expression signature that has been observed in microarray screens of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).Methods. Quantitative real-time polymerase chain reaction analysis of healthy control PBMCs was used to determine the relative induction of a panel of IFN-inducible genes (IFIGs) by IFNalpha and IFNgamma. PBMCs from 77 SLE patients were compared with those from 22 disease controls and 28 healthy donors for expression of IFIGs.Results. Expression of IFNalpha-inducible genes was significantly higher in SLE PBMCs than in those from disease controls or healthy donors. The level of expression of all IFIGs in PBMCs from SLE patients with IFNalpha pathway activation correlated highly with the inherent responsiveness of those genes to IFNalpha, suggesting coordinate activation of that cytokine pathway. Expression of genes preferentially induced by IFNgamma was not significantly increased in SLE PBMCs compared with control PBMCs. IFNalpha-regulated gene-inducing activity was detected in some SLE plasma samples.Conclusion. The coordinate activation of IFNalpha-induced genes is a characteristic of PBMCs from many SLE patients, supporting the hypothesis that IFNa is the predominant stimulus for IFIG expression in lupus.