Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
Regional Centre for Biotechnology, Faridabad, India.
PLoS One. 2023 Mar 16;18(3):e0281637. doi: 10.1371/journal.pone.0281637. eCollection 2023.
Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are the two highly prevalent debilitating and sometimes life-threatening systemic inflammatory autoimmune diseases. The etiology and pathogenesis of RA and SLE are interconnected in several ways, with limited knowledge about the underlying molecular mechanisms. With the motivation to better understand shared biological mechanisms and determine novel therapeutic targets, we explored common molecular disease signatures by performing a meta-analysis of publicly available microarray gene expression datasets of RA and SLE. We performed an integrated, multi-cohort analysis of 1088 transcriptomic profiles from 14 independent studies to identify common gene signatures. We identified sixty-two genes common among RA and SLE, out of which fifty-nine genes (21 upregulated and 38 downregulated) had similar expression profiles in the diseases. However, antagonistic expression profiles were observed for ACVR2A, FAM135A, and MAPRE1 genes. Thirty genes common between RA and SLE were proposed as robust gene signatures, with persistent expression in all the studies and cell types. These gene signatures were found to be involved in innate as well as adaptive immune responses, bone development and growth. In conclusion, our analysis of multicohort and multiple microarray datasets would provide the basis for understanding the common mechanisms of pathogenesis and exploring these gene signatures for their diagnostic and therapeutic potential.
类风湿关节炎(RA)和系统性红斑狼疮(SLE)是两种高度流行的使人虚弱且有时危及生命的全身性炎症性自身免疫性疾病。RA 和 SLE 的病因和发病机制在多个方面相互关联,对潜在的分子机制知之甚少。为了更好地了解共同的生物学机制并确定新的治疗靶点,我们通过对 RA 和 SLE 的公开微阵列基因表达数据集进行荟萃分析来探索常见的分子疾病特征。我们对来自 14 项独立研究的 1088 个转录组谱进行了综合的多队列分析,以确定共同的基因特征。我们确定了 RA 和 SLE 之间共有的 62 个基因,其中 59 个基因(21 个上调和 38 个下调)在这两种疾病中的表达模式相似。然而,ACVR2A、FAM135A 和 MAPRE1 基因的表达模式则相反。我们提出了 30 个 RA 和 SLE 之间共有的基因作为稳健的基因特征,它们在所有研究和细胞类型中都有持续表达。这些基因特征被发现参与固有和适应性免疫反应、骨发育和生长。总之,我们对多队列和多个微阵列数据集的分析将为理解共同的发病机制提供基础,并探索这些基因特征在诊断和治疗方面的潜力。