Comprehensive molecular profiling of Hispanic, Black, Asian, and White patients with atopic dermatitis via tape strip RNA sequencing and serum proteomics.

BACKGROUND

Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with known ethnic disparities in clinical presentation and treatment response. However, molecular data, particularly for Hispanic patients, remain limited.

OBJECTIVE

We sought to characterize the molecular phenotype of AD across Hispanic, Black, Asian, and White patients using tape strip transcriptomic and blood proteomic profiling.

METHODS

We enrolled 47 patients with AD (9 Hispanic, 14 Black, 11 Asian, 13 White) and 40 control subjects. Tape strips and serum were collected for RNA sequencing and proteomic analysis, respectively. Differential expression, pathway enrichment, and gene-clinical correlations were analyzed across ethnicities.

RESULTS

Across ethnicities, we identified shared immune activation in lesional and nonlesional skin in patients with AD, including upregulation of TH1-related (eg, IL12B, TNF), TH2-related (eg, CCL17, IL13), and TH17-related (eg, CXCL1/2, IL6) pathways. However, gene-level drivers varied: TH1-related markers (eg, CXCL10) were more elevated in White and Black patients, TH17 axis skewing was most pronounced in Asian patients, and TH22 and Janus kinase 3 signaling showed greater activation in White and Black patients. Hispanic patients demonstrated a mixed immune phenotype resembling AD in both White and Black patients. Barrier dysfunction, including filaggrin deficiency and lipid synthesis defects, was universal, with Asian patients exhibiting the most pronounced lipid-related gene downregulation. Proteomic data mirrored transcriptomic trends and highlighted broad systemic inflammation in Hispanic patients. White patients exhibited the strongest correlations between lesional gene expression and disease severity, though differences in clinical presentation and global scoring methods may influence these correlations across skin tones.

CONCLUSIONS

This multi-omics, multiethnic analysis reveals both shared and ethnicity-specific molecular signatures in AD, with the first in-depth profiling, to our knowledge, of Hispanic patients. These findings may inform future precision-targeted therapies across diverse populations.