类风湿关节炎亚临床滑膜炎转录组学特点

Transcriptomic features in rheumatoid arthritis patients with subclinical synovitis

目的研究与类风湿关节炎(rheumatoid arthritis,RA)亚临床滑膜炎发生相关的失调基因及通路。方法纳入存在亚临床滑膜炎及临床和超声均缓解的RA患者各5例。对所有患者进行临床、实验室及超声评估。从患者外周血分离出外周血单个核细胞,进行RNA测序、差异表达基因(differentially expressed genes,DEGs)分析、GO功能富集、KEGG通路富集和蛋白网络互作(protein-protein interaction,PPI)分析。结果与超声缓解组患者对比,亚临床滑膜炎组患者共发现304个DEGs,其中106个为上调基因,198个为下调基因。按照连接节点数排序筛选出20个枢纽基因。其中,在亚临床滑膜炎组,除基质金属酶(MMP)9表达上调外,其余枢纽基因均下调,且主要为与Ⅰ型干扰素信号通路及CXC趋化因子配体10(CXCL10)相关的基因。结论外周血MMP9升高以及Ⅰ型干扰素、CXCL10下调可能与RA亚临床滑膜炎的发生相关。

Objective To explore the dysregulated genes and their pathways and networks related to the mechanism of subclinical synovitis in rheumatoid arthritis(RA).Methods Five patients were enrolled in subclinical synovitis group and five in ultrasound-determined remission group.All the patients underwent clinical evaluation,laboratory tests,and ultrasound assessment.Peripheral blood mononuclear cells(PBMCs)were isolated from all patients.RNA-sequencing,analysis of differentially expressed genes(DEGs),GO functional enrichment,KEGG pathway enrichment,and protein-protein interaction(PPI)network were performed.Results A total of 304 DEGs,including 106 up-and 198 down-regulated genes,were identified in the RA patients with subclinical synovitis as compared to those with ultrasound-determined remission.Certain key target genes of subclinical synovitis were revealed to have a high connectivity degree by PPI analysis.All the key target genes except matrix metalloproteinase(MMP9)were down-regulated genes and majorly belonged to type I interferon(IFN)signaling and CXC chemokine ligand 10(CXCL10).Conclusion MMP9,CXCL10,and type I IFN signaling pathway may contribute to subclinical synovitis in RA patients who have achieved clinical remission.These biomarkers may be the potential targets.