Laboratoire de Mathématiques et Modélisation d'Evry, Université Paris-Saclay, CNRS, Univ Evry, Evry, France.
Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie François Jacob, Evry, France.
Int J Immunogenet. 2021 Jun;48(3):239-249. doi: 10.1111/iji.12528. Epub 2021 Jan 22.
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.
类风湿关节炎的发病机制部分得到了解释；然而，据信它是由多步骤过程引起的。免疫起始后是临床前阶段，最终将导致症状性疾病的发展。我们的目的是鉴定差异表达的基因，以突出参与类风湿关节炎发展临床前阶段的途径。研究人群包括类风湿关节炎患者的一级亲属，与普通人群相比，这些亲属患病的风险增加。对四组人群进行了全转录组分析：无自身抗体或与可能的类风湿关节炎相关症状的无症状人群（对照组）；有临床可疑关节痛、未分化关节炎或与 RA 相关的自身免疫（RA 的临床前阶段：Pc-RA）；随后发展为可分类的 RA（Pre-RA）；以及未经治疗的早期类风湿关节炎患者（RA）。确定了差异表达的基因，并进行了富集分析。功能富集分析显示，与对照组相比，Pc-RA、Pre-RA 和 RA 中差异表达基因的 31 条途径显著富集。破骨细胞途径是 RA 特有的 7 条途径之一。在 Pc-RA 和 Pre-RA 中，几个富集的途径包括 TP53 基因连接，如 P53 和 Wnt 信号通路。对与类风湿关节炎相关表型的全转录组分析可以突出在疾病发展的临床前阶段需要哪些途径。在复制研究中验证后，这些途径中的一些分子可以用于鉴定即将发生类风湿关节炎的个体的新的特异性生物标志物。
