Increased levels of lipocalin 2 in palmoplantar pustular psoriasis Kerstin Wolk a,b,c, *, Yvonne Frambach d , Arnd Jacobi e , Dagmar Wilsmann-Theis f , Sandra Phillipp a , Ellen Witte-Händel a,b , Jörg Wenzel f , Rotraut Mössner g,1 , Robert Sabat a,b,1 a Psoriasis Research and Treatment Centre, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany b Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany c Berlin-Brandenburg Centre for Regenerative Therapies, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany d Department of Dermatology, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany e Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany f Department of Dermatology and Allergy, University Medical Center, Sigmund-Freud-Str. 25, 53127 Bonn, Germany g Department of Dermatology, Georg-August-University Goettingen, Robert-Koch-Straße 40, 37075 Goettingen, Germany A R T I C L E I N F O Article history: Received 17 July 2017 Received in revised form 1 December 2017 Accepted 19 December 2017 Keywords: Skin inflammation Biomarker Psoriasis arthritis Interleukin-22 A B S T R A C T Background: Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles. Objective: To identify and characterize pathogenetic players in PPP. 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. 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-1b and further enhanced by IL-17 and TNF- a, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1b 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. Conclusions: In PPP, increased blood levels of LCN2 indicate an important activity of IL-1b in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased pro- atherosclerosis risk. © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved. 1. Introduction Palmoplantar pustular psoriasis (PPP) is a chronic immune- mediated skin disease that mainly affects women in the forth to seventh decade of life. The few available data on the prevalence rate of PPP vary between 0.01 to 0.05% for Western countries [1] and 0.1% for Japan [2]. The disease is characterized by erupting, sterile intraepidermal pustules on the palms and soles, with the pustules often located within psoriasis vulgaris (PV)-like erythem- atous and desquamating lesions [3]. In about 25% of PPP patients concomitant PV is present, and the family history for PV is positive in about 30% of cases [3,4]. Moreover, PPP is associated with comorbidities also known from PV [5]. In contrast to PV, PPP has been proposed to emanate from the eccrine gland [6,7] and is rather recalcitrant towards many drugs that are effective in the treatment of PV [3,4]. Moreover, PPP seems to differ genetically from PV. In particular, it is not associated with PSORS1, the main susceptibility loci for PV containing the alleles for HLA-Cw*6, HCR*WWCC and CDSN*5 [3,8]. With these features in mind, it has been debated, whether PPP is a form of psoriasis or a separate clinical entity [1,9,10]. Abbreviations: Ab, antibody; DLQI, dermatology quality of life index; LCN2, lipocalin 2; NGAL, neutrophil gelatinase-associated lipocalin; PBMC, peripheral blood mononuclear cells; PPP, palmoplantar pustular psoriasis; PV, psoriasis vulgaris. * Corresponding author at: Psoriasis Research and Treatment Centre, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. E-mail address: kerstin.wolk@charite.de (K. Wolk). 1 These authors are co-last authors. https://doi.org/10.1016/j.jdermsci.2017.12.018 0923-1811/ © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved. Journal of Dermatological Science 90 (2018) 68–74 Contents lists available at ScienceDirect Journal of Dermatological Science journal homepa ge: www.jdsjournal.com