IL-17A is functionally relevant and a potential therapeutic target in bullous pemphigoid.

IL-17A is functionally relevant and a potential therapeutic target in bullous pemphigoid. J Autoimmun. 2018 Sep 12;: Authors: Chakievska L, Holtsche MM, Künstner A, Goletz S, Petersen BS, Thaci D, Ibrahim SM, Ludwig RJ, Franke A, Sadik CD, Zillikens D, Hölscher C, Busch H, Schmidt E Abstract IL-17A has been identified as key regulatory molecule in several autoimmune and chronic inflammatory diseases followed by the successful use of anti-IL-17 therapy, e.g. in ankylosing spondylitis and psoriasis. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease with a high need for more specific, effective and safe treatment options. The aim of this study was to clarify the pathophysiological importance of IL-17A in BP. We found elevated numbers of IL-17A+ CD4+ lymphocytes in the peripheral blood of BP patients and identified CD3+ cells as major source of IL-17A in early BP skin lesions. IL17A and related genes were upregulated in BP skin and exome sequencing of 51 BP patients revealed mutations in twelve IL-17-related genes in 18 patients. We have subsequently found several lines of evidence suggesting a significant role of IL-17A in the BP pathogenesis: (i) IL-17A activated human neutrophils in vitro, (ii) inhibition of dermal-epidermal separation in cryosections of human skin incubated with anti-BP180 IgG and subsequently with anti-IL-17A IgG-treated leukocytes, (iii) close correlation of serum IL-17A levels and diseas...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research