Non-invasive proteome analysis of psoriatic stratum corneum reflects pathophysiological pathways and is useful for drug profiling

Summary

Background

Protein expression is disturbed in psoriatic stratum corneum. Non-invasive methods for the description of pathophysiological changes and drug profiling in psoriasis are desirable.

Objectives

Undertake large scale non-invasive protein expression studies in psoriatic stratum corneum to identify biomarkers of pathophysiological processes and use them for drug profiling.

Methods

Psoriatic stratum corneum was harvested through repetitive tape-stripping. Non-lesional and lesional stratum corneum, as well as vehicle- and drug-treated lesional stratum corneum samples were collected. Protein extracts from non-lesional 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, ELISA and Luminex technologies.

Results

MS-based methods identified 140 proteins differentially expressed in psoriatic stratum corneum. 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 Th1 cells, and of CCL2 and CCL4 attracting monocytes and dendritic cells were observed. Quantification of the Th1 and Th17 markers TNF, IL12B, IL17A and IL17F in lesional stratum corneum 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 stratum corneum.

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 stratum corneum detects key pathophysiological mechanisms and enables non-invasive drug profiling in translational medicine settings.

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