Microdialysis-based metabolomic and proteomic profiling reveals signature variations for disease severity in psoriasis

Psoriasis is a common chronic inflammatory skin disease characterized by epidermal hyperproliferation and immune dysregulation. However, local metabolic interactions remain incompletely understood, and biomarkers for disease activity and treatment response are still lacking. Current approaches such as skin biopsies or tape stripping are disruptive to the skin barrier and may cause scarring, limiting their repeated use. In contrast, microdialysis enables minimally invasive sampling of soluble mediators from intact skin. We applied untargeted proteomic and metabolomic profiling of skin microdialysates from lesional and nonlesional sites in patients with psoriasis and healthy controls to explore local pathophysiology and evaluate this technique's potential for monitoring disease severity and treatment response. Principal component analysis revealed distinct molecular signatures in psoriatic lesions, with separation by disease severity, resulting from elevated proinflammatory proteins (SERPINB3/4, FABP5), purine and pyrimidine metabolites (adenosine-5-monophosphate, 5'-cytidine monophosphate) and polyamines (spermidine and spermine). Pathway analysis confirmed upregulated nucleotide metabolism and polyamine biosynthesis alongside reduced histidine metabolism, consistent with hyperproliferation, immune activation, and barrier disruption. Importantly, lesional metabolomic profiles normalized in patients responding to systemic therapy, highlighting the utility of microdialysate profiling for tracking therapeutic efficacy. This study establishes microdialysate proteometabolomics as a minimally invasive platform for mechanistic studies, biomarker discovery, and personalized monitoring in psoriasis.