title: Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin.
abstract: BACKGROUND
  Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2) is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis.
  
  
  RESULTS
  We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects.
  
  
  CONCLUSIONS
  Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases.
authors.affiliation: Department of Dermatology and Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Patrick A M
authors.initials: PA
authors.lastname: Jansen
authors.forename: Diana
authors.initials: D
authors.lastname: Rodijk-Olthuis
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hollox
authors.forename: Marijke
authors.initials: M
authors.lastname: Kamsteeg
authors.forename: Geuranne S
authors.initials: GS
authors.lastname: Tjabringa
authors.forename: Gys J
authors.initials: GJ
authors.lastname: de Jongh
authors.forename: Ivonne M J J
authors.initials: IM
authors.lastname: van Vlijmen-Willems
authors.forename: Judith G M
authors.initials: JG
authors.lastname: Bergboer
authors.forename: Michelle M
authors.initials: MM
authors.lastname: van Rossum
authors.forename: Elke M G J
authors.initials: EM
authors.lastname: de Jong
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Andrea W M
authors.initials: AW
authors.lastname: Evers
authors.forename: Mieke
authors.initials: M
authors.lastname: Bergers
authors.forename: John A L
authors.initials: JA
authors.lastname: Armour
authors.forename: Patrick L J M
authors.initials: PL
authors.lastname: Zeeuwen
authors.forename: Joost
authors.initials: J
authors.lastname: Schalkwijk
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid; D015415:Biomarkers / Q000097:blood; D003876:Dermatitis, Atopic / Q000097:blood; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000175:diagnosis*; D012867:Skin / Q000098:blood supply; D023083:beta-Defensins / Q000097:blood*
chemical_list: D015415:Biomarkers; C106641:DEFB4A protein, human; D023083:beta-Defensins