Methods: RNA-sequencing (RNA-seq) was performed on biopsies taken from nonlesional, non-sunexposed upper extremity skin obtained from 10 S. aureus colonized (ADStaph+), 10 non-colonized (ADStaph-) AD subjects and 10 nonatopic (NA) Staph- controls. We report differentially expressed genes based on a false discovery rate (FDR) q-value≤0.05 using EdgeR. Gene ontology analysis was performed using the Gene Set Enrichment Analysis (GSEA) to identify KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways.
Results: RNA-seq analysis revealed a distinct transcriptional profile in ADStaph+ subjects compared to ADStaph- subjects, which were not identified in AD (Staph+ and Staph-) vs NA. Forty-seven genes were dysregulated with 40 up-regulated and 7 down-regulated in ADStaph+. Four of the 40 genes are strongly linked to Th2 inflammation (CCL18, POSTN, CCL13, CCL26). GSEA revealed 20 KEGG pathways (Familywise-error rate; P<0.04) with cytokine/cytokine receptor, T cell receptor signaling, and chemokine signaling being the most over-represented. Validation studies are underway.
Conclusions: Our findings demonstrate a dysregulation of inflammatory genes, enriched for expression of Th2 pathway genes, in the nonlesional skin of ADStaph+ subjects. The challenge will be to determine whether this is responsible for or the consequence of bacterial colonization and/or disease severity.