PBMC transcriptomic signatures reflect immune dynamics and disease activity in psoriatic arthritis

Objective: 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. Methods: 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. Results: PsA showed extensive transcriptional alterations relative to healthy individuals, characterized by activation of adaptive immune pathways, cytokine signaling, and coordinated metabolic adjustments. Compared with PsO, PsA exhibited pronounced dysregulation of extracellular matrix components, platelet activation, coagulation, and complement pathways, indicating systemic involvement not observed in skin-limited disease. Disease activity was associated with enhanced angiogenesis, cell adhesion, cell adhesion and migration, and extracellular matrix remodeling, alongside enrichment of PI3K-Akt, MAPK, IL-17, and complement/coagulation signaling. Paired longitudinal profiling demonstrated substantial transcriptomic reversibility after treatment, including attenuation of immune, stromal, and vascular signatures. Across analyses, recurrent patterns emerged: pervasive peripheral immune activation, distinct vascular and hemostatic alterations differentiating PsA from PsO, and consistent metabolic remodeling with partial normalization following therapy. Conclusion: 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.