Expression of a pathogen-response program in peripheral blood cells defines a subgroup of Rheumatoid Arthritis patients
Expression of a pathogen-response program in peripheral blood cells defines a subgroup of Rheumatoid Arthritis patients
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DOI：
10.1038/sj.gene.6364438
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发表时间：
2008-01-01
影响因子：
5
通讯作者：
Verweij, C. L.
中科院分区：
文献类型：
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作者：
van der Pouw Kraan, T. C. T. M.;van Baarsen, L. G. M.;Verweij, C. L.
类风湿性关节炎（RA）是一种病因不明的异质性疾病。在这里，我们的目的是根据外周血 (PB) 基因表达谱与病原体反应转录程序的比较来区分 RA 亚型。 PB 取自 35 名 RA 患者和 15 名健康个体。对于表达谱分析，我们使用 DNA 微阵列。对 RA 和对照样本以及病毒感染模型样本进行的组合聚类分析表明，RA 患者亚组 (RA(A)) 的基因表达谱与痘病毒感染的猕猴的基因表达谱相似。统计分析和随后对 RA(A) 患者进行的基因本体分析证实，这些患者形成了一个独特的群体，激活了几种类似于常见宿主-病原体反应的宿主防御机制。对 RA(A) 患者中过度表达的基因启动子区域的分析揭示了 NF kappa B 和干扰素激活转录因子的转录因子结合位点的富集。此外，该亚组的 RA 患者表达的抗环瓜氨酸肽抗体滴度显着增加。我们得出的结论是，宿主-病原体反应的激活定义了一个以瓜氨酸蛋白自身反应性增加为特征的 RA 患者亚组。
Rheumatoid arthritis (RA) is a heterogeneous disease with unknown etiology. Here we aimed to distinguish RA subtypes based on peripheral blood (PB) gene expression profiles in comparison with a pathogen-response transcriptional program. PB was obtained from 35 RA patients and 15 healthy individuals. For expression profiling we used DNA microarrays. A combined cluster analysis of RA and control samples together with samples from a viral infection model revealed that the gene expression profile of a subgroup of RA patients (RA(A)) was reminiscent to that of poxvirus-infected macaques. Statistical analysis, followed by Gene Ontology analysis of the RA(A) patients confirmed that these patients form a distinct group, with activation of several host defense mechanisms that resemble a common host-pathogen response. Analysis of the promoter region of genes that were overexpressed in the RA(A) patients, revealed an enrichment of transcription factor binding sites for NF kappa B and interferon-activated transcription factors. Moreover, this subgroup of RA patients expressed significantly increased titers of anti-cyclic citrullinated peptide antibodies. We conclude that activation of a host-pathogen response defines a subgroup of RA patients characterized by increased autoreactivity against citrullinated proteins.