title: Lipocalin-2 is expressed by activated granulocytes and keratinocytes in affected skin and reflects disease activity in acne inversa/hidradenitis suppurativa.
abstract: BACKGROUND
  Acne inversa (AI)/hidradenitis suppurativa is a chronic inflammatory disease characterized by painful axillary, inguinal and perianal skin lesions with deep-seated nodules, abscesses and fistulae.
  
  
  OBJECTIVE
  This study aimed to identify and characterize the key players in AI pathogenesis.
  
  
  METHODS
  Epidemiological and anamnestic data for patients with AI were collected, and blood and skin samples were also taken. Healthy participants and patients with psoriasis served as controls. Assessment of samples and cultures of primary cells was performed by enzyme-linked immunosorbent assay, quantitative polymerase chain reaction on reverse transcribed mRNA, and immunohistochemistry.
  
  
  RESULTS
  Of 35 mediators quantified in the blood of patients with AI, lipocalin-2 (LCN2) appeared as one of the most significantly upregulated parameters compared with healthy participants [85·8 ± 12·2 (n = 18) vs. 41·8 ± 4·2 (n = 15); P < 0·001]. Strongly elevated LCN2 expression was present in AI lesions, with granulocytes and keratinocytes being sources of this expression. In vitro, these cells upregulated LCN2 production in response to tumour necrosis factor (TNF)-α, and a positive relationship between systemic TNF-α and LCN2 levels (rs= 0·55, P = 0·011; n = 20) was evident for AI. LCN2 blood levels correlated with AI disease severity (rs= 0·65, P < 0·001; n = 29), but not with disease duration, age, sex, body mass index or smoking habit. Detailed analyses revealed a link with the number of skin regions containing nodules and fistulae, but not scars.
  
  
  CONCLUSIONS
  LCN2 might serve as a blood biomarker for the objective assessment of inflammatory activity in AI. We suggest a self-amplification loop comprising TNF-α, neutrophilic granulocytes and LCN2, which contributes to the recurrent skin neutrophil infiltration in AI, clinically evident as pus.
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Charité University Medicine, Berlin, Germany.|Psoriasis Research and Treatment Centre, Dermatology/Medical Immunology, Charité University Medicine, Berlin, Germany.|Berlin-Brandenburg Centre for Regenerative Therapies, Charité University Medicine, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wolk
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wenzel
authors.affiliation: Psoriasis Research and Treatment Centre, Dermatology/Medical Immunology, Charité University Medicine, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Tsaousi
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Charité University Medicine, Berlin, Germany.|Psoriasis Research and Treatment Centre, Dermatology/Medical Immunology, Charité University Medicine, Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Witte-Händel
authors.affiliation: Institute of Medical Immunology, Charité University Medicine, Berlin, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Babel
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Charité University Medicine, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Zelenak
authors.affiliation: Berlin-Brandenburg Centre for Regenerative Therapies, Charité University Medicine, Berlin, Germany.|Institute of Medical Immunology, Charité University Medicine, Berlin, Germany.
authors.forename: H-D
authors.initials: HD
authors.lastname: Volk
authors.affiliation: Department of Dermatology and Allergy, Charité University Medicine, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Sterry
authors.affiliation: Department of Dermatology and Allergy, Charité University Medicine, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schneider-Burrus
authors.affiliation: Interdisciplinary Group of Molecular Immunopathology, Charité University Medicine, Berlin, Germany.|Psoriasis Research and Treatment Centre, Dermatology/Medical Immunology, Charité University Medicine, Berlin, Germany.|Research Centre Immunosciences, Charité University Medicine, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Sabat
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006098:Granulocytes / Q000378:metabolism*; D017497:Hidradenitis Suppurativa / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D000071068:Lipocalin-2 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration / Q000502:physiology; D012867:Skin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D014409:Tumor Necrosis Factor-alpha