CCR5 + T cells as a potential biomarker for primary Sjögren's disease based on bioinformatics analysis

To identify and verify potential biomarkers for primary Sjögren's disease (pSjD) using bioinformatics analysis and explore the molecular immune mechanisms of biomarkers.male-to-female ratio of 1:9 METHODS: The pSjD datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and functional analysis were conducted. PPI network analysis was performed and the hub genes were screened by Cytoscape software. The diagnostic value was assessed by receiver operating characteristic (ROC) analysis. To explore biomarker-immune cell relations, we used CIBERSORT for cell-type identification, combined with scRNA-seq data. Lastly, we validated the expression of the biomarker in human samples.

A total of 96 overlapping genes, including 1 downregulated and 95 upregulated genes, were obtained. Based on the enrichment analysis, these overlapping genes were mapped to terms related to the functions and regulation of the immune system. CCR5 was identified as a critical biomarker and demonstrated high diagnostic accuracy for pSjD. From CIBERSORT analysis, CCR5 was significantly associated with diverse immune cells. Further scRNA-seq analysis indicated that CCR5 was specifically upregulated in T cells of pSjD salivary gland tissues, which was confirmed in pSjD patients.

Our findings show the role of CCR5 in pSjD, mediated by immune mechanisms. CCR5 is localized in T cells of pSjD salivary glands. Elevated CCR5 expression may be a key biomarker, and increased CCR5 + T cells could aid future diagnosis, prognosis, and treatment of pSjD.