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复发缓解型、原发进展型和继发进展型多发性硬化症的基因表达分析。

Gene expression analysis of relapsing-remitting, primary progressive and secondary progressive multiple sclerosis.

机构信息

Danish Multiple Sclerosis Center, Denmark.

出版信息

Mult Scler. 2013 Dec;19(14):1841-8. doi: 10.1177/1352458513500553. Epub 2013 Oct 1.

Abstract

BACKGROUND

Previous studies of multiple sclerosis (MS) have indicated differences in the pathogenesis in relapsing-remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS) disease.

OBJECTIVE

We hypothesized that different MS subtypes would show differences in gene expression that could be traced to specific subsets of peripheral blood mononuclear cells (PBMCs).

METHODS

Gene expression in RRMS, SPMS, PPMS and healthy control (HC) PBMCs was analyzed on Affymetrix arrays. In addition, we studied gene expression in pools of purified PBMC subsets.

RESULTS

We found 380 genes that were differentially expressed in RRMS, PPMS, SPMS and HCs (false discovery rate < 5%). There were no major differences between the subtypes of MS. The genes showing most prominent expression changes in RRMS were associated with adaptive immune pathways, while genes in PPMS were associated with innate immune system pathways. SPMS patients shared pathways with RRMS and PPMS patients. Gene expression changes were most prominent in B cells, CD8+ T cells and monocytes.

CONCLUSION

Differences in gene expression, which could be traced to B cells, CD8+ T cells and monocytes, were found between MS patients and HCs but only minor differences were observed between MS subgroups.

摘要

背景

先前关于多发性硬化症(MS)的研究表明,在复发缓解型(RRMS)、继发进展型(SPMS)和原发进展型(PPMS)疾病中,其发病机制存在差异。

目的

我们假设不同的 MS 亚型会表现出基因表达的差异,这些差异可以追溯到特定的外周血单核细胞(PBMC)亚群。

方法

我们使用 Affymetrix 微阵列分析 RRMS、SPMS、PPMS 和健康对照组(HC)PBMC 的基因表达。此外,我们还研究了 PBMC 亚群的纯化池中的基因表达。

结果

我们发现了 380 个在 RRMS、PPMS、SPMS 和 HCs 中差异表达的基因(错误发现率 < 5%)。MS 各亚型之间没有明显差异。RRMS 中表达变化最明显的基因与适应性免疫途径有关,而 PPMS 中的基因与固有免疫系统途径有关。SPMS 患者与 RRMS 和 PPMS 患者共享途径。基因表达变化在 B 细胞、CD8+T 细胞和单核细胞中最为明显。

结论

MS 患者与 HC 之间存在 B 细胞、CD8+T 细胞和单核细胞等基因表达的差异,但在 MS 亚组之间观察到的差异较小。

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