Gene Expression Profiling in Dermatitis Herpetiformis SkinLesions

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated with gluten-sensitive enteropathy (CD). Inorder to investigate the pathogenesis of skin lesions at molecular level, we analysed the gene expression profiles in skin biopsiesfrom 6 CD patients with DH and 6 healthy controls using Affymetrix HG-U133A 2.0 arrays. 486 genes were differentiallyexpressed in DH skin compared to normal skin: 225 were upregulated and 261 were downregulated. Consistently with theautoimmune origin of DH, functional classification of the differentially expressed genes (DEGs) indicates a B- and T-cell immuneresponse (LAG3, TRAF5, DPP4, and NT5E). In addition, gene modulation provides evidence for a local inflammatory response(IL8, PTGFR, FSTL1, IFI16, BDKRD2, and NAMPT) with concomitant leukocyte recruitment (CCL5, ENPP2), endothelial cellactivation, and neutrophil extravasation (SELL, SELE). DEGs also indicate overproduction of matrix proteases (MMP9, ADAM9,and ADAM19) and proteolytic enzymes (CTSG, ELA2, CPA3, TPSB2, and CMA1) that may contribute to epidermal splitting andblister formation. Finally, we observed modulation of genes involved in cell growth inhibition (CGREF1, PA2G4, and PPP2R1B),increased apoptosis (FAS, TNFSF10, and BASP1), and reduced adhesion at the dermal epidermal junction (PLEC1, ITGB4, andLAMA5). In conclusion, our results identify genes that are involved in the pathogenesis of DH skin lesions