title: Noninvasive proteome analysis of psoriatic stratum corneum reflects pathophysiological pathways and is useful for drug profiling.
abstract: BACKGROUND
  Protein expression is disturbed in the psoriatic stratum corneum (SC). Noninvasive methods for the description of pathophysiological changes and drug profiling in psoriasis are desirable.
  
  
  OBJECTIVE
  Undertake large-scale noninvasive protein expression studies in psoriatic SC to identify biomarkers of pathophysiological processes and use them for drug profiling.
  
  
  METHODS
  Psoriatic SC was harvested through repetitive tape-stripping. Nonlesional and lesional SC, as well as vehicle-treated and drug-treated lesional SC samples were collected. Protein extracts from nonlesional and lesional skin biopsies were used for comparison. Calcipotriol-betamethasone (CB) was used as a reference medication. Proteins extracted from pooled tape strips were quantified using mass spectrometry (MS), Western blotting, enzyme-linked immunosorbent assay and Luminex technologies.
  
  
  RESULTS
  MS-based methods identified 140 proteins differentially expressed in psoriatic SC. Epidermis development, glycolysis, regulation of apoptosis, cytoskeleton organization and peptide cross-linking were modulated, all reflecting perturbed epidermal differentiation. Using antibody-based techniques, increased levels of sICAM1, of CXCL1- and CXCL8-attracting neutrophils, of CXCL10- and CCL4-attracting T helper (Th) 1 cells, and of CCL2- and CCL4-attracting monocytes and dendritic cells were observed. Quantification of the Th1 and Th17 markers tumour necrosis factor, interleukin (IL) 12B, IL17A and IL17F in lesional SC was successful, while the Th2 cytokines IL4, IL5 and IL13, not involved in the disease process, were not detected. The pruritic cytokine IL31 was detected in lesional SC. CXCL1, CXCL8, CXCL10 and sICAM were used to investigate disease remission, ranking three topical treatments according to their known clinical efficacy.
  
  
  CONCLUSIONS
  Protein biomarker quantification in psoriatic SC detects key pathophysiological mechanisms and enables noninvasive drug profiling in translational medicine settings.
authors.affiliation: Galderma R&D, 2400, route des colles, 06410, Biot, France.
authors.forename: B
authors.initials: B
authors.lastname: Méhul
authors.affiliation: Galderma R&D, 2400, route des colles, 06410, Biot, France.
authors.forename: G
authors.initials: G
authors.lastname: Laffet
authors.affiliation: Galderma R&D, 2400, route des colles, 06410, Biot, France.
authors.forename: A
authors.initials: A
authors.lastname: Séraïdaris
authors.affiliation: Galderma R&D, 2400, route des colles, 06410, Biot, France.
authors.forename: L
authors.initials: L
authors.lastname: Russo
authors.affiliation: 132 rue d'Assas 75006, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Fogel
authors.affiliation: Galderma R&D, 2400, route des colles, 06410, Biot, France.
authors.forename: I
authors.initials: I
authors.lastname: Carlavan
authors.affiliation: Galderma R&D, 2400, route des colles, 06410, Biot, France.
authors.forename: C
authors.initials: C
authors.lastname: Pernin
authors.affiliation: Galderma R&D, 2400, route des colles, 06410, Biot, France.
authors.forename: P
authors.initials: P
authors.lastname: Andres
authors.affiliation: Centre de Pharmacologie Clinique Appliquée à la Dermatologie (CPCAD), University Hospital of Nice, 5 rue Pierre Devoluy, 06000, Nice, France.
authors.forename: C
authors.initials: C
authors.lastname: Queille-Roussel
authors.affiliation: Galderma R&D, 2400, route des colles, 06410, Biot, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Voegel
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology; D004817:Epidermis / Q000737:chemistry*; D006801:Humans; D009000:Monocytes / Q000502:physiology; D020556:Neutrophil Infiltration / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D020543:Proteome / Q000737:chemistry*; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D018417:Th1 Cells / Q000502:physiology; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019743:Chemokines, CXC; D016207:Cytokines; D011506:Proteins; D020543:Proteome; D016211:Transforming Growth Factor alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A