Increased levels of lipocalin 2 in palmoplantar pustular psoriasis

Background: Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles.& para;& para;Objective: To identify and characterize pathogenetic players in PPP.& para;& para;Methods: Clinical and anamnestic data as well as skin and blood samples of 60 PPP patients were collected. Healthy participants served as controls. Analysis of patient samples and cultured primary skin cells was performed by ELISA, qRT-PCR, and immunohistochemistry.& para;& para;Results: Upon screening of blood mediators in PPP patients, lipocalin 2 (LCN2) emerged as being significantly upregulated compared to healthy participants. LCN2 blood levels were independent of age, sex, or concomitant psoriasis vulgaris. Keratinocytes in PPP skin lesions were important LCN2 producers. In vitro, LCN2 production of these cells was upregulated by IL-1 beta and further enhanced by IL-17 and TNF alpha, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1 beta and LCN2 levels was evident in PPP. LCN2 blood levels also showed a positive correlation with PPP pustule score, Dermatology Quality of Life Index and blood levels of the pro-atherogenic molecule resistin.& para;& para;Conclusions: In PPP, increased blood levels of LCN2 indicate an important activity of IL-1 beta in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased proatherosclerosis risk. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.