Lymphocyte-Platelet and Neutrophil-Platelet Aggregates are Associated with Dysregulated Platelet Inflammatory Pathways in Psoriasis

Background Psoriasis is a chronic immune-mediated inflammatory disease associated with heightened cardiovascular risk. Platelets are increasingly implicated in this link through their capacity to amplify vascular inflammation and interact with leukocytes. Circulating leukocyte–platelet aggregates are elevated in psoriasis, although the biological significance of these aggregates remains incompletely understood. We investigated whether increased leukocyte–platelet aggregates is associated with alterations in the platelet transcriptomic profile in psoriasis. Methods Leukocyte–platelet aggregate levels were compared between psoriasis patients (n = 42) and healthy controls (n = 29). Psoriasis patients were stratified by the cohort median lymphocyte-platelet aggregate (LyPA) or neutrophil-platelet aggregate (NPA) levels into high vs low aggregate groups. Platelet RNA sequencing was then performed to define transcriptomic differences in high-vs low-aggregate psoriasis. Results Psoriasis patients (mean age 46; 60% male; 81% Caucasian) had higher LyPA ( P = 0.001) and NPA ( P = 0.04) compared with healthy controls (mean age 42; 55% male; 69% Caucasian). Platelet RNA sequencing revealed that psoriasis patients with high LyPA or high NPA had downregulation of platelet inflammatory pathways, including interferon, tumor necrosis factor (TNF), IL-8, and IL-6 signaling. Conclusion These findings identify inflammatory platelet transcriptomic alterations associated with elevated lymphocyte-platelet and neutrophil-platelet aggregates in psoriasis and motivate further work to define the functional consequences of leukocyte-platelet aggregates in psoriasis.