Differential expressions and potential clinical values of lncRNAs in the plasma exosomes of rheumatoid arthritis

• Published in: International immunopharmacology 2024-02, Vol.128, p.111511, Article 111511
• Main Authors: Shuai, Zi-Qiang, Wang, Zhi-Xin, Ren, Jia-Le, Yang, Xiao-Ke, Xu, Bin
• Format: Article
• Language: English
• Subjects: Biomarker; Long non-coding RNA (lncRNA); Plasma exosome; Rheumatoid arthritis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111511

•New research on exsomal lncRNAs in RA patients reveals a promising avenue for RA diagnostic and therapies.•The results showed that lncRNA SNHG6, RPS18P9, and CXXC4-AS1 had potential role in disease.•ROC analysis reveals excellent performance of lncRNA SNHG6, RPS18P9, and CXXC4-AS1 as biomarkers (AUC: 0.847-0.994). Rheumatoid arthritis (RA) is a common autoimmune disease with unclear pathogenesis. Progress in its clinical diagnosis and treatment mainly depends on the elucidation of its pathogenesis and the exploration of new biomarkers. Exosomes contain various biomolecules, including long non-coding ribonucleic acids (lncRNAs). lncRNAs may participate in the regulation of autoimmune and inflammatory processes during RA pathogenesis by transmitting these biomolecules via exosomes among different cells. Therefore, the investigation of lncRNAs in RA exosomes may be a feasible pathway to elucidate RA pathogenesis, identify new diagnostic biomarkers, and identify potential therapeutic targets. In the first phase of exosomal non-coding RNAs screening, exosomes were isolated from the peripheral blood of six patients with RA and healthy controls (HC). High-throughput RNA sequencing was performed to obtain lncRNA expression profiles, and 15 lncRNAs with the highest differential expression were selected as candidate lncRNAs. In the second phase of validation using real-time quantitative polymerase chain reaction (qRT-PCR), differential expression of the 15 candidate lncRNAs was verified in 42 patients with RA and their matched HC. Their potential value as RA diagnostic biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Their relationships with common clinical indices of RA were explored using Spearman’s rank correlation and linear regression analyses. Compared to HC, patients with RA had 206 upregulated and 2,332 downregulated lncRNAs. Fifteen candidate lncRNAs were validated by qRT-PCR, of which 12 (SNHG6, RPS18P9, RPL21P28, EBLN3P, FAM153CP, RPL23P8, SNHG31, NORAD, H3P6, DLEU2, TUG1, and OIP5-AS1) were upregulated, and three (CXXC4-AS1, OLMALINC, and NPHP3-AS1) were downregulated. In the ROC analysis of the 15 candidate lncRNAs, the area under the curve (AUC) ranged from 0.847 (0.767, 0.927) for OLMALINC to 0.994 (0.984, 1.000) for CXXC4-AS1. Spearman rank correlation analysis revealed erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score of 28 (DAS28) were correlated with seven, six, and fiv