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Noninvasive proteome analysis of psoriatic stratum corneum reflects pathophysiological pathways and is useful for drug profiling
Author(s) -
Méhul B.,
Laffet G.,
Séraïdaris A.,
Russo L.,
Fogel P.,
Carlavan I.,
Pernin C.,
Andres P.,
QueilleRoussel C.,
Voegel J.J.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15346
Subject(s) - psoriasis , medicine , cytokine , cxcl1 , immunology , pathology , chemokine , inflammation
Summary 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. Objectives 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 sICAM 1, of CXCL 1‐ and CXCL 8‐attracting neutrophils, of CXCL 10‐ and CCL 4‐attracting T helper (Th) 1 cells, and of CCL 2‐ and CCL 4‐attracting monocytes and dendritic cells were observed. Quantification of the Th1 and Th17 markers tumour necrosis factor, interleukin ( IL ) 12B, IL 17A and IL 17F in lesional SC was successful, while the Th2 cytokines IL 4, IL 5 and IL 13, not involved in the disease process, were not detected. The pruritic cytokine IL 31 was detected in lesional SC . CXCL 1, CXCL 8, CXCL 10 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.