类风湿性关节炎(RA)管理倾向于实现缓解或低疾病活动。在这项研究中,我们对36例患者(18例RA患者和18例配对对照者)的外周血单个核细胞(PBMC)进行了单细胞RNA测序(scRNAseq),考虑年龄,性别,种族,和种族),以确定疾病相关的细胞亚群和与疾病活动相关的细胞类型特异性特征。我们的分析揭示了18个不同的PBMC子集,包括IFITM3过表达干扰素激活(IFN激活)的单核细胞亚群。我们观察到中度至高度疾病活动性(DAS28-CRP≥3.2)患者的CD4+T效应记忆细胞增加,低疾病活动性或缓解期患者的非经典单核细胞减少(DAS28-CRP<3.2)。通过细胞类型的Pseudobulk分析确定了RA和匹配对照之间的168个差异表达基因,随着γ-δT细胞亚群中促炎基因的下调,IFN激活亚群中与RA易感性相关的基因改变,和非经典单核细胞。此外,我们发现了一个与中度-高度疾病活动性相关的基因标记,以TNF等促炎基因上调为特征,JUN,EGR1,IFIT2,MAFB,G0S2和下调包括HLA-DQB1、HLA-DRB5、TNFSF13B的基因。值得注意的是,细胞间通讯分析揭示了信号通路的上调,包括VISTA,在中高和缓解低疾病活动环境中。我们的发现为RA疾病活动的全身细胞和分子机制提供了有价值的见解。
Rheumatoid arthritis (RA) management lean toward achieving remission or low-disease activity. In this study, we conducted single-cell RNA sequencing (scRNAseq) of peripheral blood mononuclear cells (PBMCs) from 36 individuals (18 RA patients and 18 matched controls, accounting for age, sex, race, and ethnicity), to identify disease-relevant cell subsets and cell type-specific signatures associated with disease activity. Our analysis revealed 18 distinct PBMC subsets, including an IFITM3 overexpressing Interferon-activated (IFN-activated) monocyte subset. We observed an increase in CD4+ T effector memory cells in patients with moderate to high disease activity (DAS28-CRP ≥ 3.2), and a decrease in non-classical monocytes in patients with low disease activity or remission (DAS28-CRP < 3.2). Pseudobulk analysis by cell type identified 168 differentially expressed genes between RA and matched controls, with a downregulation of pro-inflammatory genes in the gamma-delta T cells subset, alteration of genes associated with RA predisposition in the IFN-activated subset, and non-classical monocytes. Additionally, we identified a gene signature associated with moderate-high disease activity, characterized by upregulation of pro-inflammatory genes such as TNF, JUN, EGR1, IFIT2, MAFB, G0S2, and downregulation of genes including HLA-DQB1, HLA-DRB5, TNFSF13B. Notably, cell-cell communication analysis revealed an upregulation of signaling pathways, including VISTA, in both moderate-high and remission-low disease activity contexts. Our findings provide valuable insights into the systemic cellular and molecular mechanisms underlying RA disease activity.