The Distinct Monocyte Subsets and Intercellular Communication in Primary Sjögren's Syndrome Revealed by Single-Cell RNA Sequencing.

OBJECTIVE: The presence of unique monocyte subsets and sub-populations plays a significant role in the onset and progression of rheumatic diseases. This study aimed to characterize variations in monocyte subsets and sub-populations and functional roles in patients with primary Sjögren's syndrome (pSS) using single-cell RNA sequencing (scRNA-seq). METHOD: Monocyte samples from patients with pSS and healthy controls (HCs) were analyzed using single-cell RNA sequencing (scRNA-seq). This approach identified divergent gene expression patterns, transcription factors, and immune cells interactions within monocyte subset and sub-populations, highlighting pathways potentially involved in the pathogenesis of pSS. RESULTS: The scRNA-seq analysis delineated three major monocyte subsets: classical monocytes (CD14++CD16-), non-classical monocytes (CD14-CD16+), and cDC2, with further identification of sub-populations within the classical and non-classical monocyte subsets. A notable increase in the proportions of classical monocyte sub-population 2 and non-classical monocyte sub-population 2 was observed in pSS patients. Compared to the HCs, pSS patients exhibited enhanced immune cell interactions within monocyte subsets. Furthermore, in pSS patients, the dominant increased pathways within monocytes were those related to viral responses, interferon activity, and oxidative phosphorylation. Additionally, significantly elevated expression levels of IFI44, IFI44L, HBA2, LY6E, XAF1, EPSTI1, APOBEC3A, and IFIT3 were identified in pSS monocytes. CONCLUSION: This research revealed irregular alterations in monocyte subsets and sub-populations, transcription factors, and gene expression patterns within pSS patients, pinpointing prospective biomarkers in pSS as viable targets for therapeutic intervention.