To characterize systemic transcriptomic alterations across psoriatic arthritis (PsA) disease states, including distinctions from psoriasis-only (PsO), signatures of disease activity, and treatment-responsive changes in peripheral blood mononuclear cells.

RNA sequencing was performed in patients with PsA, psoriasis without arthritis (PSO) and healthy controls (HC). Four analytical comparisons were examined: PsA versus healthy controls, PsA versus PsO, active versus remission PsA, and paired pre- versus post-treatment PsA. Differential gene expression(DEGs), functional enrichment, and protein-protein interaction analyses were integrated to delineate immune and metabolic programs across conditions.

1. Comparison of PsA vs. HC: A total of 3,412 differentially expressed genes (DEGs) were identified. Analysis revealed extensive activation of adaptive immune pathways (e.g., T cell receptor signaling pathway) and cytokine signaling in patients with PsA, accompanied by remodeling of metabolic programs such as oxidative phosphorylation and fatty acid metabolism.

2. Comparison of PsA vs. PsO: Forty-nine DEGs were identified. Compared with PsO, PsA exhibited distinctive dysregulation of extracellular matrix organization, platelet activation, coagulation, and complement pathways, suggesting systemic vascular and hemostatic abnormalities distinct from cutaneous-limited psoriasis.

3. Comparison of active vs. inactive PsA: Seventy-nine DEGs were identified. Disease activity was significantly associated with angiogenesis, cell adhesion, migration, and activation of signaling pathways including PI3K-Akt, MAPK, and IL-17. PPI network analysis further highlighted hub genes related to endothelial activation (e.g., CDH5, KDR).

4. Comparison of pre- vs. post-treatment: A total of 2,336 DEGs were detected after treatment, among which 1,352 genes showed reversed expression toward the healthy baseline. Changes in immune signaling pathways (e.g., PI3K-Akt, coagulation) and selected metabolism-related genes (e.g., GLUD2, AMY2B) indicated that treatment partially reversed immune-stromal activation and metabolic dysregulation

This multi-dimensional transcriptomic study delineates immune, vascular, and metabolic perturbations across PsA disease states and highlights their dynamic modulation with disease activity and treatment. These findings provide an integrated framework for understanding systemic inflammatory patterns in PsA and support future mechanistic and translational investigation.