Comparative gene expression analysis in Asian atopic dermatitis and psoriasis: Identifying key molecular targets for precision therapy

Summary: Abstract Body: Atopic dermatitis (AD) and psoriasis are chronic inflammatory skin diseases characterized by distinct immune and molecular signatures. However, in clinical practice, differentiating between AD and psoriasis can be particularly challenging in Asian patients due to overlapping or atypical clinical features. This study aimed to delineate differentially expressed genes (DEGs) and associated pathways in lesional skin samples from Asian patients with AD and psoriasis to identify potential diagnostic/therapeutic targets. Transcriptomic analysis was performed on skin samples from six AD patients, seven psoriasis patients, and twelve healthy controls. A total of 6,445 DEGs were identified. Functional enrichment analysis revealed distinct immune signatures, with Th2 cell differentiation predominating in AD and Th17 cell differentiation in psoriasis. Additionally, pathways related to keratinization and epidermal differentiation were elevated in both AD and psoriasis, suggesting a shared inflammatory mechanism. Among these, 52 genes demonstrating the most significant differential expression were selected for further analysis. Among these, filaggrin (FLG) expression was significantly reduced in both AD (P=0.0116) and psoriasis (P=0.0002) compared to controls. Serine protease inhibitor Kazal-type 5 (SPINK5) expression was elevated in psoriasis (P<0.001) but showed a downward trend in AD. Loricrin (LOR) expression was significantly decreased in AD (P=0.0031) and psoriasis (P=0.0021), while Serine family B member 4 (SERPINB4) expression was substantially upregulated in both AD (P<0.0001) and psoriasis (P<0.0001), which were validated by immunofluorescence staining. Key genes such as FLG, SPINK5, LOR, and SERPINB4 reflect the unique molecular mechanisms of AD and psoriasis in Asian patients. These findings provide critical insights into the disease pathogenesis and a foundation for novel diagnostic/therapeutic strategies. Hye Li Kim^{1, 2}, Dong Eun Kim¹, Kelun zhang¹, Su Min Kim¹, Tae-Gyun Kim¹, Chang Ook Park^{1, 2} 1. Department of Dermatology, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of). 2. Yonsei University Brain Korea 21 Project for Medical Science, Seodaemun-gu, Seoul, Korea (the Republic of). Adaptive and Auto-Immunity