β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis.

Background IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. Objective We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A–driven pathology. Methods We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti–IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases. Results IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P P P r  = 0.70, n = 199, P r  = 0.53, n = 281, P Conclusion IL-17A is a primary driver of skin pathology in patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A–driven skin pathology.