T cell gene expression profiling identifies distinct subgroups of Japanese multiple sclerosis patients
T cell gene expression profiling identifies distinct subgroups of Japanese multiple sclerosis patients
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DOI：
10.1016/j.jneuroim.2006.02.004
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发表时间：
2006-05-01
影响因子：
3.3
通讯作者：
Yamamura, Takashi
中科院分区：
文献类型：
--
作者：
Satoh, Jun-ichi;Nakanishi, Megumi;Yamamura, Takashi
为了阐明多发性硬化症（MS）异质性的分子背景，我们利用cDNA芯片分析了MS和健康对照（CN）受试者外周血CD3+ T细胞的基因表达谱。在阵列上的1258个cdna中，有286个基因在72名未治疗的日本MS患者和22名年龄和性别匹配的CN受试者之间表达差异。当将该集合用作分层聚类分析的判别器时，它识别出MS患者的4个不同亚组以及亚组间差异表达的5个基因簇。其中一个基因簇在MS与CN中过度表达，并且在临床最活跃的MS亚组中特别增强。在46名MS患者接受干扰素- β (IF β -1b)治疗两年之后，IFN β应答者聚集在四个MS亚组中的两个。此外，在开始IFN治疗后的3个月和6个月，IFN应答者与无应答者在IFN应答基因的动力学上有所不同。这些结果表明，t细胞基因表达谱对于识别与不同疾病活动性和IFN β治疗反应相关的MS不同亚组是有价值的。(c) 2006 Elsevier B.V.版权所有
To clarify the molecular background underlying the heterogeneity of multiple sclerosis (MS), we characterized the gene expression profile of peripheral blood CD3+ T cells isolated from MS and healthy control (CN) subjects by using a cDNA microarray. Among 1258 cDNAs on the array, 286 genes were expressed differentially between 72 untreated Japanese MS patients and 22 age- and sex-matched CN subjects. When this set was used as a discriminator for hierarchical clustering analysis, it identified four distinct subgroups of MS patients and five gene clusters differentially expressed among the subgroups. One of these gene clusters was overexpressed in MS versus CN, and particularly enhanced in the clinically most active subgroup of MS. After 46 of the MS patients were treated with interferon-beta (IF beta-1b) for two years, IFN beta responders were clustered in two of the four MS subgroups. Furthermore, the IFN beta responders differed from nonresponders in the kinetics of IFN-responsive genes at 3 and 6 months after starting IFN beta treatment. These results suggest that T-cell gene expression profiling is valuable to identify distinct subgroups of MS associated with differential disease activity and therapeutic response to IFN beta. (c) 2006 Elsevier B.V. All rights reserved.