Background: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are among the most prevalent inflammatory rheumatic musculoskeletal disorders (I-RMDs). These disorders are characterized by inflammation of the synovium and/or the axial skeleton, which is driven by dysregulated interactions between the innate and adaptive immune systems. V-domain Ig suppressor of T cell activation (VISTA) is an inhibitory checkpoint that functions as both a receptor and a ligand. It is highly expressed on antigen-presenting cells (APCs) and T cells, which place it at the interface between innate and adaptive immunity. However, its expression in I-RMDs remains poorly defined.

Objectives: The objective of this study was to map VISTA expression in the peripheral blood of patients with RA, PsA, and axSpA.

Methods: This exploratory study included bionaïve, sex-matched patients with RA (n=49), PsA (n=50), axSpA (n=49), as well as healthy controls (HC,n=49). Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. VISTA mRNA expression was quantified in PBMC-pellets using qPCR. Expression of cell-surface VISTA and its ligands (VSIG-8, PSGL-1) on immune cells was assessed by flow cytometry. Soluble VISTA (sVISTA) serum concentrations were quantified using ELISA. Group comparisons were performed using nonparametric statistical tests.

Results: mRNA expression was significantly elevated in RA (p<0.001) and PsA (p<0.05) vs. in axSpA, whereas axSpA patients showed levels comparable to HCs. The most prominent differences in VISTA surface expression were observed on conventional monocytes and CD4+ T cells, with statistical significance observed only when comparing RA and axSpA. Preliminary data on VSIG-8 and PSGL-1 surface expression suggest an I-RMD-specific pattern across monocytes, T-cells and dendritic cells. Serum sVISTA concentrations were significantly elevated in both RA and axSpA compared to HCs, whereas PsA showed no significant differences in levels relative to HCs.

Conclusions: VISTA exhibits distinct mRNA, cellular, and soluble expression patterns across peripheral I-RMDs, indicating specific regulation of this inhibitory checkpoint at the intersection of innate and adaptive immunity. These findings suggest that VISTA may modulate inflammatory pathways differently in RA, PsA, and axSpA, warranting further studies to investigate its functional role and its potential as a biomarker of specific disease phenotypes

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: Iulia Roman: None declared, Brikena Lalazi: None declared, Styliani Tsiami: None declared, Uta Kiltz Novartis, AbbVie, Amgen, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, GSK, Grünenthal, Hexal, Janssen, MSD, Pfizer, Roche, UCB, Viatris, Biocad, Novartis, AbbVie, Amgen, Biogen, Chugai, Eli Lilly, Fresenius, Gilead, GSK, Grünenthal, Hexal, Janssen, MSD, Pfizer, Roche, UCB, Viatris, Laura Ney: None declared, Xenofon Baraliakos AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, AbbVie, BMS, Chugai, Novartis, Pfizer, UCB, MSD, AbbVie, Novartis, Christian Schütz Novartis.