Skin biomarkers of hidradenitis suppurativa/acne inversa

Daifallah Almansouri1, Christos C. Zouboulis1,2

1Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany
2European Hidradenitis Suppurativa Foundation e.V., Dessau, Germany

Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory disease of the follicular portion of the folliculopilosebaceous unit mediated by many non-specific inflammatory cytokines including IL17, IL23, IL1 and TNFα. However, recently demonstrated signal pathways indicate the complexity of HS pathogenesis. In this study we investigate the expression and localization of the transglutaminase inhibitory proteins (SERPINB3/B4) and the antimicrobial proteins (S100A7-A9) in HS by gene array analysis, qRT-PCR and immunohistochemistry. Comparative analysis of gene expression in the lesional vs healthy appearing skin from microarray data of 8 affected patients and 4 healthy individuals showed 705 statistically significant upregulated and 482 downregulated genes (fold change>2, p<0.05). In relation to the biopsies taken from control individuals, 994 genes were upregulated and 1046 downregulated. Overexpression of the keratocyte proteins SERPINB3/B4 and S100A7/A8/A9 was validated using qRT-PCR. SERPINB4 and S100A8/A9 were overexpressed in the lesional skin vs. non-lesional with average fold changes of 18.5, 23.0, and 28.3, respectively (n =15). Immunohistochemistry staining showed an upregulation of these proteins in lesional skin, specifically in the epidermis as well as in the inner and outer sheath of hair follicle. Our findings may implicate new pathways in the pathogenesis of HS, which are associated with interruption of essential cellular functions, e.g. protein cross linking at the terminal differentiation level of follicular keratinocytes.

Upregulation of SERPINB3/B4 and S100A7-9 in hidradenitis suppurativa / acne inversa