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 kappaB 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.

中文翻译：

---

外周血细胞中病原体反应程序的表达定义了类风湿关节炎患者的一个亚组。

类风湿关节炎（RA）是一种病因不明的异质性疾病。在这里，我们旨在根据与病原体反应转录程序相比，外周血（PB）基因表达谱来区分RA亚型。PB获自35名RA患者和15名健康个体。对于表达谱，我们使用了DNA微阵列。RA和对照样品以及病毒感染模型样品的组合聚类分析显示，RA患者亚组（RA（A））的基因表达谱与经痘病毒感染的猕猴的基因表达谱相似。进行统计分析，然后对RA（A）患者进行基因本体分析，证实这些患者形成了独特的群体，并激活了几种类似于常见宿主-病原体反应的宿主防御机制。分析在RA（A）患者中过表达的基因的启动子区域，发现NF kappaB和干扰素激活的转录因子的转录因子结合位点富集。而且，该RA患者亚组表达抗环瓜氨酸肽抗体的滴度显着增加。我们得出结论，宿主-病原体反应的激活定义了以抗瓜氨酸化蛋白的自身反应性增强为特征的RA患者亚组。