Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures.
Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures.
复制标题
DOI：
10.1002/art.38628
复制
发表时间：
2014-06
影响因子：
13.3
通讯作者：
Chaussabel, Damien
中科院分区：
文献类型：
--
作者：
Chiche, Laurent;Jourde-Chiche, Noemie;Whalen, Elizabeth;Presnell, Scott;Gersuk, Vivian;Dang, Kristen;Anguiano, Esperanza;Quinn, Charlie;Burtey, Stephane;Berland, Yvon;Kaplanski, Gilles;Harle, Jean-Robert;Pascual, Virginia;Chaussabel, Damien
干扰素（IFN）-α在系统性红斑狼疮（SLE）发病机制中的作用得到基因表达研究的有力支持。本研究的目的是改善成人SLE患者血液IFN特征的表征。前瞻性招募并随访连续性患者。使用Illumina珠芯片生成微阵列数据。一个模块化的转录库被用作分析的框架。我们的260个模块的库，其中包括共聚类的基因集，包括3个IFN-注释的模块（M1.2，M3.4和M5.12），强烈上调SLE患者。在54/62（87%）例患者或131/157（83%）例纵向样本中观察到模块化IFN签名（mIS）。IFN特征比预期的更复杂，每个模块显示出不同的激活阈值（M1.2<M3.4<M5.12），因此提供了基于存在0、1、2或3个活性IFN模块对SLE患者进行分层的模块评分。在临床静止期患者中观察到类似的mIS梯度，与无/轻度模块评分（0或1个活性IFN模块）的患者相比，中度/强模块评分（2或3个活性IFN模块）与较高的抗dsDNA滴度和较低的淋巴细胞计数相关。纵向分析显示，在单个患者中，随时间推移mIS的稳定（M1.2）和可变（M3.4和M5.12）组分。有趣的是，对其他数据集的挖掘表明，M3.4和M5.12也可能由INF-β和γ驱动。模块库分析揭示了SLE中复杂的IFN特征，不仅限于先前的IFN-α特征，还涉及β和γ IFN。
The role for interferon (IFN)-α in systemic lupus erythematosus (SLE) pathogenesis is strongly supported by gene expression studies. The aim of this study was to improve characterization of the blood-IFN signature in adult SLE patients. Consecutive patients were enrolled and followed-up prospectively. Microarray data were generated using Illumina beadchips. A modular transcriptional repertoire was employed as a framework for the analysis. Our repertoire of 260 modules, which consist of co-clustered gene sets, included 3 IFN-annotated modules (M1.2, M3.4 and M5.12) that were strongly up-regulated in SLE patients. A modular IFN signature (mIS) was observed in 54/62 (87%) patients or 131/157 (83%) longitudinal samples. The IFN signature was more complex than expected with each module displaying a distinct activation threshold (M1.2<M3.4<M5.12), thus providing a modular score to stratify SLE patients based on the presence of 0, 1, 2 or 3 active IFN modules. A similar gradient in mIS was observed within clinically quiescent patients, for whom moderate/strong modular scores (2 or 3 active IFN modules) were associated with higher anti-dsDNA titers and lower lymphocyte count than patients with absent/mild modular scores (0 or 1 active IFN modules). Longitudinal analyses revealed both stable (M1.2) and variable (M3.4 and M5.12) components of mIS over time in single patients. Interestingly, mining of other datasets suggested that M3.4 and M5.12 could be also driven by INF-β and γ. Modular repertoire analysis reveals complex IFN signatures in SLE, not restricted to the previous IFN-α signature, but involving also β and γ IFNs.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.4
作者：
Kropp, Kai A.;Robertson, Kevin A.;Ghazal, Peter
通讯作者：
Ghazal, Peter
影响因子：
--
作者：
Bauer, Jason W.;Petri, Michelle;Batliwalla, Franak M.;Koeuth, Thearith;Wilson, Joseph;Slattery, Catherine;Panoskaltsis-Mortari, Angela;Gregersen, Peter K.;Behrens, Timothy W.;Baechler, Emily C.
通讯作者：
Baechler, Emily C.
使用基于途径的方法对微阵列数据进行荟萃分析确定了人类外周血单核细胞中全身性红斑狼疮的37基因表达签名。
影响因子：
9.3
作者：
Arasappan D;Tong W;Mummaneni P;Fang H;Amur S
通讯作者：
Amur S
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V