Conjunctival MicroRNA expression signature in primary Sjögren's syndrome dry eye: a NanoString-based bioinformatic analysis

Purpose: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by inflammation and tissue destruction of the salivary and lacrimal glands, leading to sicca symptoms. Dysregulation of microRNAs (miRNAs), key post-transcriptional regulators, has been implicated in pSS, but their role in conjunctival epithelial cells (CECs) remains unclear. This study aimed to identify altered miRNA expression patterns in CEC from patients with pSS and their potential involvement in pSS pathogenesis. Methods: CEC samples were collected from six patients with pSS and six healthy controls (HCs) using nylon-tipped swabs. The miRNA expression was profiled using the NanoString nCounter system with minimal RNA input. Differentially expressed (DE) miRNAs were identified via ROSALIND software, and bioinformatics tools (miRNet and miRTargetLink) were applied to construct miRNA-centric networks, predict target genes, and perform pathway enrichment analysis. Results: We identified 11 DE miRNAs in patients with pSS compared with the HCs. Key miRNAs, including hsa-miR-548j-3p and hsa-miR-219b-3p, are central to immune and inflammatory regulation pathways. Pathway enrichment analysis highlighted their involvement in processes such as immune cell regulation, inflammatory signaling, and glandular damage. Dysregulated miRNAs modulate key targets, like TNFAIP3, IL6R, IFNAR1, IL7, and ICOSLG, suggesting their potential role in pSS pathogenesis. Conclusions: This study underscores the potential of miRNAs as biomarkers and therapeutic targets in pSS-associated dry eye disease. Despite limitations like small sample size and reliance on in silico predictions, our findings provide valuable insights into miRNA-mediated regulation of immune responses and inflammation, paving the way for future diagnostic and therapeutic advancements.