The etiopathogenesis of rheumatoid arthritis is partially understood; however, it is believed to result from a multi-step process. The immune onset followed by pre-clinical phases will eventually lead to the development of symptomatic disease. We aim at identifying differentially expressed genes in order to highlight pathways involved in the pre-clinical stages of rheumatoid arthritis development. The study population consisted of first-degree relatives of patients with rheumatoid arthritis, known to have an increased risk of developing disease as compared to the general population. Whole transcriptome analysis was performed in four groups: asymptomatic without autoantibodies or symptoms associated with possible rheumatoid arthritis (controls); having either clinically suspect arthralgias, undifferentiated arthritis or autoimmunity associated with RA (pre-clinical stages of RA: Pcs-RA); having subsequently developed classifiable RA (pre-RA); and early untreated rheumatoid arthritis patients (RA). Differentially expressed genes were determined, and enrichment analysis was performed. Functional enrichment analysis revealed 31 pathways significantly enriched in differentially expressed genes for Pcs-RA, pre-RA and RA compared to the controls. Osteoclast pathway is among the seven pathways specific for RA. In Pcs-RA and in pre-RA, several enriched pathways include TP53 gene connections, such as P53 and Wnt signalling pathways. Analysis of whole transcriptome for phenotypes related to rheumatoid arthritis allows highlighting which pathways are requested in the pre-clinical stages of disease development. After validation in replication studies, molecules belonging to some of these pathways could be used to identify new specific biomarkers for individuals with impending rheumatoid arthritis.

中文翻译：

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通过基因表达谱鉴定特定于类风湿性关节炎发展前阶段的生物途径

类风湿性关节炎的发病机制已部分了解；然而，据信这是一个多步骤过程的结果。临床前阶段的免疫发作最终将导致有症状的疾病的发展。我们的目标是识别差异表达的基因，以突出类风湿性关节炎发展的临床前阶段所涉及的途径。研究人群由类风湿性关节炎患者的一级亲属组成，已知与普通人群相比，患类风湿性关节炎的风险增加。对四组进行全转录组分析：无自身抗体或与可能的类风湿性关节炎相关的症状的无症状组（对照组）；有临床怀疑的关节痛，与 RA 相关的未分化关节炎或自身免疫（RA 的临床前阶段：Pcs-RA）；随后开发了可分类的 RA（前 RA）；和早期未经治疗的类风湿性关节炎患者 (RA)。确定差异表达的基因，并进行富集分析。功能富集分析显示，与对照组相比，31 条通路显着富集了 Pcs-RA、pre-RA 和 RA 的差异表达基因。破骨细胞通路是 RA 特有的七种通路之一。在 Pcs-RA 和 pre-RA 中，几种富集的通路包括 TP53 基因连接，例如 P5​​3 和 Wnt 信号通路。对与类风湿性关节炎相关表型的全转录组分析可以突出显示在疾病发展的临床前阶段需要哪些途径。