Blood transcriptional signatures of multiple sclerosis: Unique gene expression of disease activity
Blood transcriptional signatures of multiple sclerosis: Unique gene expression of disease activity
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DOI：
10.1002/ana.20008
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发表时间：
2004-03-01
影响因子：
11.2
通讯作者：
Mandel, M
中科院分区：
文献类型：
--
作者：
Achiron, A;Gurevich, M;Mandel, M
多发性硬化症 (MS) 是一种中枢神经系统疾病，其病程和结果不可预测。外周血单核细胞（PBMC）参与疾病发病机制并诱导活性脱髓鞘。使用寡核苷酸微阵列，我们在 26 名多发性硬化症患者的 PBMC 中鉴定出了具有统计显着性的 1,109 个基因的转录特征，无论疾病激活状态或免疫调节治疗如何。该特征包含涉及 MS 发病机制的潜在过程的基因，包括 T 细胞激活和扩增、炎症和细胞凋亡。与细胞募集、表位扩散和逃避监管免疫监视有关的 721 个基因的另一个转录特征识别出急性复发与缓解的多发性硬化症患者。我们的结果为理解 MS 涉及的机制提供了新的机会，并表明 PBMC 中的基因表达模式包含有关远程目标疾病过程的信息，这可能有助于 MS 的诊断和未来治疗策略的制定。
Multiple sclerosis (MS) is a central nervous system disease with an unpredictable course and outcome. Peripheral blood mononuclear cells (PBMCs) are involved in the disease pathogenesis and induce active demyelination. Using oligonucleotide microarrays, we identified a statistically significant transcriptional signature of 1,109 genes in PBMCs from 26 MS patients, irrespective of disease activation state or immunomodulatory treatment. This signature contains genes that implicate underlying processes involved in MS pathogenesis including T-cell activation and expansion, inflammation, and apoptosis. Another transcriptional signature of 721 genes involved in cellular recruitment, epitope spreading, and escape from regulatory immune surveillance identified MS patients in acute relapse compared with remission. Our results offer new opportunity for understanding the mechanisms involved in MS and indicate that gene expression patterns in PBMCs contain information about a remote-target disease process that may be useful for diagnosis and future tailoring of therapeutic strategies for MS.