VNN2-expressing circulating monocytes exhibit unique functional characteristics and are decreased in patients with primary Sjögren's syndrome

Objective: This study aims to elucidate the significance of VNN2 expression in peripheral blood monocytes and its clinical relevance in primary Sjögren's syndrome (pSS).

Methods: We investigated VNN2 expression by analyzing single-cell RNA sequencing (scRNA-seq) data from peripheral blood mononuclear cells. Flow cytometry was used to detect and compare VNN2 expression in total monocytes, classical monocytes (cMo), intermediate monocytes (iMo) and non-classical monocytes (ncMo). Additionally, we examined the expression of HLA, ICAM1, CD62L, ITGAM, S100A8, S100A9, CCR2, CCR6, CX3CR1 and CXCR3 in VNN2⁺ and VNN2^- cells. We analyzed the correlation between VNN2 expression and clinical indicators and assessed the clinical utility of VNN2⁺ monocytes in pSS diagnosis using receiver operating characteristic curves.

Results: We observed high VNN2 expression in monocytes, with significantly higher levels in CD14⁺⁺ monocytes compared to ncMo. VNN2⁺ monocytes exhibited decreased expression of HLA and CD62L and increased expression of ICAM1, ITGAM, S100A8, S100A9, CCR2, CCR6, CX3CR1 and CXCR3 compared to VNN2^- monocytes. Although scRNA-seq data showed that VNN2 mRNA was upregulated, cell surface expression of VNN2 was decreased in monocytes from pSS patients compared to healthy controls. The reduced levels of VNN2⁺ monocyte subpopulations in pSS patients were negatively correlated with anti-ribosome antibody levels and positively correlated with complement 4 levels. Detection of VNN2 expression in monocytes can aid in the auxiliary diagnosis of pSS.

Conclusion: Monocytes expressing cell surface VNN2 are significantly reduced in pSS patients. This suggests a potential role for VNN2 in pSS development and its potential use as a diagnostic marker for pSS.