Introduction Psoriasis (PSO) is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and dysregulated activation of the IL-23/IL-17 axis, leading to persistent cutaneous inflammation and substantial disease burden. Comprehensive profiling of circulating inflammatory proteins provides important insights into the systemic immune alterations associated with PSO and its treatment. However, the longitudinal plasma proteomic changes induced by IL-17A blockade remain incompletely characterized. Methods We quantified the expression levels of 92 inflammation-related proteins in plasma samples from 10 patients with moderate-to-severe PSO before and during secukinumab therapy, as well as from 10 healthy controls (NC), using the Olink Target 96 Inflammation panel. Key differentially expressed proteins were further validated by enzyme-linked immunosorbent assay (ELISA). Longitudinal patterns were assessed using Mfuzz clustering, and functional enrichment analyses were performed to explore the underlying biological pathways. Results Baseline plasma proteomic profiles clearly discriminated PSO patients from healthy individuals, with CXCL1, CXCL5, CCL20, and HGF exhibiting the most pronounced alterations and the highest diagnostic performance. Longitudinal analysis revealed a coordinated reduction of multiple inflammatory mediators following IL-17A inhibition, including CCL20, IL-17C, IL-6, and OSM. Mfuzz analysis identified two dominant temporal expression patterns characterized by a progressive decrease in inflammatory and immune-related proteins over the course of secukinumab treatment. Notably, baseline circulating IL-17C levels were significantly positively correlated with disease severity, suggesting its potential as a biomarker of therapeutic response. Functional enrichment analysis indicated that differentially expressed proteins (DEPs) were mainly involved in cytokine–cytokine receptor interaction and IL-17-related signaling pathways. Discussion To our knowledge, this is the first study to characterize the longitudinal plasma proteomic landscape of PSO patients treated with secukinumab using the Olink platform. This work provides molecular evidence for the systemic immunomodulatory effects of IL-17A blockade and highlights candidate circulating biomarkers for disease monitoring and treatment response in PSO. Given the small sample size, these results should be validated in larger, independent cohorts.
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