Cross-sectional study of proteomic differences between moderate and severe psoriasis

Background: Although there is an ongoing understanding of psoriasis vulgaris (PV) pathogenesis, little is known about the proteomic diversity of psoriatic lesions between moderate and severe psoriasis. Objective: To evaluate the proteomic differences between moderate and severe psoriasis and determine biomarkers associated with disease severity. Methods: In this cross-sectional study, we report a proteomic analysis of psoriatic lesions from patients with severe PV (sPV group, n=7) using data-independent acquisition mass spectrometry (DIA-MS), as compared with patients with moderate psoriasis (mPV group, n=8). Results: 173 differentially expressed proteins (DEPs) were significantly differentially expressed between the sPV and mPV groups. Among them, 85 proteins were upregulated, while 88 were downregulated (FC ≥±1.5, P <0.05). Eighteen DEPs were mainly enriched in the IL−17 signalling pathway, Neutrophil extracellular trap formation, Neutrophil degranulation and NF−kappa B signalling pathway, which were associated with psoriasis pathogenesis. Ingenuity pathway (IPA) analysis identified TNF and TDP53 as the top upstream up-regulators, while Lipopolysaccharide and YAP1 were the top potential down-regulators. The main active pathways were antimicrobial peptides and PTEN signalling, while the inhibitory pathways were the neutrophil extracellular trap pathway, neutrophil degranulation, and IL-8 signalling. 4D-parallel reaction monitoring (4D-PRM) analysis suggested that KRT6A were downregulated in sPV.