Interleukin-17A immune pattern across genetic acantholytic and blistering disorders

Interleukin (IL)-17A was highly expressed in all samples of Hailey-Hailey disease, Darier disease, and junctional and dystrophic epidermolysis bullosa. These results suggest that IL-17A does play a role in the pathogenesis of inflammation in acantholytic and blistering genodermatoses. Therefore anti-IL-17A therapy should be considered as an alternative or additional treatment for patients with these genodermatoses. There is a high therapeutic need in acantholytic and blistering genodermatoses. Cutaneous inflammation is a reasonable therapeutic target, although the patterns are not yet fully elucidated. Here we investigated by immunohistochemistry whether interleukin (IL)-17A is expressed in the inflammatory infiltrate in 34 patients with Hailey-Hailey disease, Darier disease, and junctional and dystrophic epidermolysis bullosa. There was a 5-7-fold increase in the number of IL-17A-positive cells in all patients' samples as compared with normal skin. IL-17A cells were present in epidermal acantholytic areas and dermal inflammatory infiltrates in Hailey-Hailey and Darier disease. In epidermolysis bullosa samples, positive cells were present at the dermoepidermal junction zone. The IL-17A inflammatory pattern was validated by observing upregulation of downstream genes/proteins, S100A7, S100A8 and S100A9 (S100 calcium-binding proteins). These results suggest that IL-17A contributes to skin inflammation and could be a therapeutic target during inflammatory flares in these disorders.