Evaluation of skin-surface interleukin 1 alpha, interleukin-1 Receptor Antagonist, CXCL-1/2 and  beta-defensin-1 as non-invasive biomarkers for monitoring psoriasis vulgaris

Abstract

Background: Psoriatic skin is typically evaluated through visual assessment of its clinical hallmarks: thickness, redness and scaling of skin lesions. Sonography is used to physically monitor disease severity through physical assessment of the skin outer layers. Both methods assess consequences of inflammation rather than the molecular basis of disease. The aim of the current study was to assess 1) whether expression patterns of IL-1α, IL-1RA, CXCL-1, CXCL-2, and hBD-1, examples of proteins known to drive psoriasis pathology, can be measured non-invasively from the skin surface, 2) whether expression patterns of these proteins correlate with disease severity, and 3) whether skin surface expression of these proteins can be used to measure pharmacodynamic effects of psoriasis treatment. Results: Using non-invasive FibroTx TAP technology for sampling and measurements of proteins from the skin of psoriasis patients revealed clear differences of IL-1α, IL-1RA, CXCL-1/2 on lesional skin when compared to non-lesional skin or skin from healthy volunteers. Comparing these expression patterns with visual assessment of thickness, redness and scaling of skin lesions revealed no significant quantitative correlations, with the exception of a weak correlation between CXCL-1/2 and thickness of lesions. Similarly, there were no significant correlations between FibroTx TAP measurements and ultrasound measurements, with the exception of a weak correlation between CXCL-1/2 and SLEB thickness. The potential of these skin-surface biomarkers were studied by monitoring skin lesions of psoriasis patients undergoing narrow-band UVB (311 nm) phototherapy. During the course of UVB treatment, clear patterns towards normalisation of IL-1RA and CXCL-1/2 were observed on lesions measured. Conclusions: Skin surface measurements of proteins involved in psoriasis skin pathology, in this study exemplified by IL-1α, IL-1RA, CXCL-1/2 and hBD-1, have potential as biomarkers for monitoring severity of disease, as well as for monitoring pharmacodynamic changes. Skin surface measurements of IL-1RA and CXCL-1/2 displayed a different profile than achieved by visual scoring of local inflammation or sonography, thus confirming that measuring the ‘molecular root’ of inflammation appears to have value as an objective, non-invasive biomarker measurement for scoring disease severity in its own right.