Longitudinal plasma proteomics identifies diagnostic and response-associated inflammatory and immune biomarkers in psoriasis following secukinumab therapy

IntroductionPsoriasis (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.MethodsWe 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.ResultsBaseline 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.