Sex-Based Transcriptomic Differences in Psoriatic Lesions: A Comprehensive Meta-Analysis

Psoriasis, a chronic inflammatory skin disease affecting men and women equally, presents distinct gender-based differences in severity and treatment response. While molecular mechanisms underlying psoriasis are well-studied, sex-specific differences remain largely unexplored. To address this, we conducted a meta-analysis of transcriptomic data from lesional psoriasis skin and healthy controls, comparing male and female cohorts. Our findings reveal 2,760 overlapping differentially expressed genes (DEGs) between sexes, highlighting shared pathways like IL-17 signaling and Th17 differentiation. However, sex-specific pathways emerged, including male-enriched PI3K-Akt signaling and chemokine receptor activity, and female-enriched glycolysis and AHR-NRF2 pathways. Upstream regulator analysis identified sex-specific drivers, including VEGFA activation and CFTR inhibition in males, and AHR activation and FGF21 inhibition in females. Notably, Tregs and neutrophil abundance differed by sex, aligning with disease severity trends. These results highlight critical molecular and cellular disparities, emphasizing the need for personalized, sex-specific therapeutic approaches in psoriasis management.