436 Lipocalin-2 as a novel biomarker in Acne inversa

Abstract

436 Lipocalin-2 as a novel biomarker in Acne inversa K Wolk, E Witte, A Tsaousi, K Witte, H Volk, W Sterry, J Wenzel, S Schneider-Burrus and R Sabat 1 Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charite, Berlin, Germany, 2 Berlin-Brandenburg Center for Regenerative Therapies, University Hospital Charite, Berlin, Germany, 3 Department of Dermatology and Allergy, University Hospital Charite, Berlin, Germany and 4 Department of Dermatology and Allergy, University of Bonn, Bonn, Germany Acne inversa (AI) patients present with painful and disabling cutaneous nodules, abscesses, fistulae and extensive scarring, typically situated within the large humid skin folds of the axillary, inguinal, perianal and/or submammary areas. In addition, AI patients frequently suffer from metabolic, endocrinological, and psychological morbidities. The high burden of patients contrasts with the fragmentary understanding of underlying pathogenetic processes and the lack of biomarkers reflecting the inflammatory state. To illuminate this issue we individually quantified the levels of 40 parameters in the blood of AI patients including proteins and microRNAs. These analyses revealed lipocalin-2 (LCN2) to be most significantly upregulated. Regarding the cellular sources, we demonstrated that neutrophilic granulocytes, abundant in AI lesions, secreted LCN2 especially after TNFa stimulation. Furthermore, LCN2 production was evident for keratinocytes in response to TNFa with amplifying contribution of IL-17A, but not for fibroblasts or endothelial cells. Accordingly, LCN2 levels positively correlated with systemic TNFa levels in AI. LCN2 blood levels also positively correlated with the disease severity. In-depth analyses revealed a link between LCN2 blood levels and the number of regions with inflammatory nodes and fistulas, but not with the number of scars. Functionally, we found evidences for a role of LCN2 in cardiovascular alterations as deduced from the correlation between LCN2 and both resistin and chemerin blood levels. In summary, we demonstrate elevated LCN2 levels in skin lesions and blood of AI patients, shed light on their cellular sources, suggest their role in metabolic comorbidities, and recommend LCN2 as blood biomarker for AI disease activity. 437 Integrated molecular and morphological characterization of psoriasis skin provides insights into disease mechanisms U Wehkamp, F Degenhardt, E Rodriguez, H Baurecht, N Volks, F Thielking, A Franke and S Weidinger 1 Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany and 2 Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany Skin global gene expression profiling has indicated the presence of distinct gene expression signatures in patients with inflammatory skin diseases such as atopic dermatitis and psoriasis. However, many studies suffer from small sample sizes, imperfect patient and biopsy matching, and limitations related to the use of microarray technologies. We here assessed the cutaneous transcriptomal architecture in 28 patients and 39 healthy controls matched for age, sex and site of biopsy using next generation sequencing generating w26 million (median) paired-end reads per sample. We performed a differential gene expression (DEG) analysis using DESeq2 adjusting for age, gender and experimental conditions. Functional annotation was performed using the R-package goseq and the Gene Ontology database. DEGs were defined by absolute log2 fold-change (FC) of above 1 and a Benjamini-Hochberg corrected pvalue of below 0.05. The absolute number of detected genes ranged between 23.000 and 29.000. Digital image analysis was performed including total cell count, CD3, CD8 and neutrophil elastase expression in relation to epidermal and dermal area. First analyses identified 11 and 5554 transcripts differentially expressed in non-lesional psoriasis (PN) versus healthy skin (NN) and lesional psoriasis (PL) versus NN (11/2104 upand 0/3450 downregulated), respectively. In non-lesional psoriatic skin, upregulated genes were related to epidermal differentiation and neutrophil aggregation. These genes were further strongly upregulated in PL with an approx. 5 fold log2FC. Compared to PN, in PL also an upregulation of multiple genes associated with Th17 inflammation and neutrophil chemotaxis and aggregation was observed. Currently pathway and gene co-expression network analysis as well as correlation analysis with tissue composition based on computer-aided quantitative analysis of digital images is being performed.