Differences in the expression of long noncoding RNAs in peripheral blood mononuclear cells indicate potential biomarkers for rheumatoid arthritis

Int Immunopharmacol. 2024 May 10:134:112218. doi: 10.1016/j.intimp.2024.112218. Online ahead of print.

Abstract

Objective: Long noncoding RNAs (lncRNAs) play an increasingly important role in various autoimmune diseases. We aimed to characterize the expression profiles of lncRNAs in peripheral blood mononuclear cells (PBMCs) from RA patients and to assess the potential of these lncRNAs as RA biomarkers.

Methods: Whole-transcriptome sequencing was used to establish a lncRNA expression profile. A total of 155 RA patients, 145 healthy controls, 59 systemic lupus erythematosus (SLE) patients and 59 primary Sjögren's syndrome (pSS) patients were recruited for this study. Four candidate lncRNAs (linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7) were validated via qRT-PCR in independent samples, and their expression, association with RA clinical features and value as RA biomarkers were evaluated.

Results: Linc00152 and lnc-ADM-1 exhibited upregulated expression (p = 0.001, p = 0.014, respectively), while ITSN1-2 and lnc-FTH1-7 exhibited downregulated expression (both p < 0.001, respectively) in RA patients compared to controls. Lnc-ADM-1 and lnc-FTH1-7 expression correlated positively with the C4 level (p = 0.016 and p = 0.012, respectively). ITSN1-2 levels were negatively associated with CRP levels (p = 0.024). Linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7 showed potential as RA biomarkers, with the four-lncRNA panel distinguishing RA patients from controls, SLE patients, or pSS patients (AUC = 0.886, 0.746, and 0.749, respectively).

Conclusion: The altered expression of linc00152, lnc-ADM-1, ITSN1-2 and lnc-FTH1-7 in RA patients suggested that these genes may serve as potential biomarkers for RA and could be involved in its pathogenesis.

Keywords: Biomarker; Rheumatoid arthritis; Transcriptome sequencing; long noncoding RNA.