MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis

https://doi.org/10.1016/j.jdermsci.2014.05.005Get rights and content

Highlights

  • MicroRNAs are detectable in whole blood, plasma and PBMCs from patients with psoriasis.

  • We identified significant changes in the miRNome of blood from patients with psoriasis.

  • miR-223 and -143 expressions in PBMCs correlate with psoriasis disease severity (PASI).

  • miR-223 and -143 are candidates as early biomarkers for psoriasis treatment response.

Abstract

Background

Psoriasis is a systemic inflammatory skin disease. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that recently have been found in the blood to be relevant as disease biomarkers.

Objective

We aimed to explore miRNAs potential as blood biomarkers for psoriasis.

Methods

Using microarray and quantitative real-time PCR we measured the global miRNA expression in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) from patients with psoriasis and healthy controls.

Results

We identified several deregulated miRNAs in the blood from patients with psoriasis including miR-223 and miR-143 which were found to be significantly upregulated in the PBMCs from patients with psoriasis compared with healthy controls (FCH = 1.63, P < 0.01; FCH = 2.18, P < 0.01, respectively). In addition, miR-223 and miR-143 significantly correlated with the PASI score (r = 0.46, P < 0.05; r = 0.55, P < 0.02, respectively). Receiver-operating characteristic analysis (ROC) showed that miR-223 and -143 have the potential to distinguish between psoriasis and healthy controls (miR-223: area under the curve (AUC) = 0.80, miR-143: AUC = 0.75). Interestingly, after 3–5 weeks of treatment with methotrexate following a significant decrease in psoriasis severity, miR-223 and miR-143 were significantly downregulated in the PBMCs from patients with psoriasis.

Conclusion

We suggest that changes in the miR-223 and miR-143 expressions in PBMCs from patients with psoriasis may serve as novel biomarkers for disease activity in psoriasis; however, further investigations are warranted to clarify their specific roles.

Introduction

Psoriasis is a chronic inflammatory disease of the skin [1]. Several attempts have been made to identify soluble biomarkers for psoriasis, however; there are still no specific biomarkers that can accurately predict disease progression and therapeutic response [2], [3], [4]. Hence, biomarkers for prognosis, response to treatment and even biomarkers related to comorbidities are needed to improve patient management and outcomes. MicroRNAs (miRNAs) are an abundant class of highly conserved small non-coding RNA molecules that modulate gene expression post-transcriptionally [5], [6], [7]. MicroRNAs act primarily within the cell, however; recent evidence has shown the presence of miRNAs in cell-free environments, including serum and plasma [8], [9] where they have proved stable and resistant to degradation of RNAses [10]. Thus, since the initial description of circulating miRNAs [8], [10], [11], [12] many efforts have been made to explore whether miRNAs can be used as diagnostic and prognostic tools for various diseases [13]. At present, the origin and biological significance of circulating miRNA still remain elusive; however, most circulating miRNAs may actually derive from blood cells [14], exosomes [15], apoptotic bodies [16], high-/low density lipoprotein [17] and/or RNA-binding proteins [18], [19]. Earlier studies on psoriasis-specific miRNA expression were primarily confined to skin tissue samples [20], [21], [22] and we have previously shown that changes in miRNA expression in the skin can be used as a diagnostic biomarker for skin diseases [23]. A few studies have investigated the miRNA expression in sera from patient with psoriasis [24], [25] and demonstrated that anti-TNFα therapy had a profound effect on the serum level of a number of miRNAs [26].

In this study we aimed to analyze the miRNA expression in different blood compartments from patients with psoriasis and healthy controls to explore miRNAs potential as blood biomarkers for psoriasis. We identified several deregulated miRNAs in the blood from patients with psoriasis among others miR-223 and miR-143 in the PBMCs from patients with psoriasis. Altogether our results suggest that changes in the miRNA expression in the blood from patients with psoriasis may become novel biomarkers for psoriasis.

Section snippets

Materials and methods

Detailed protocols are described in [50], [51].

MicroRNA expression in whole blood from patients with psoriasis

By collecting whole blood directly into a stabilizing agent that prevent further RNA transcription and degradation we sought to explore if the miRNA expression in whole blood can be used as a biomarker for psoriasis by capturing the miRNome at the time of blood collection. From 24 patients with mild to moderate psoriasis (PASI < 8) and 15 healthy controls we measured the global miRNA expression in whole blood. Clinical and demographic features are summarized in Table S2. In agreement with prior

Discussion

We undertook an explorative and comprehensive analysis of the miRNA expression in different blood compartments from patients with psoriasis and healthy controls aiming to explore the miRNAs potential to serve as blood biomarkers for psoriasis. We are, to our knowledge, the first to investigate the global miRNA expression in whole blood, plasma and PBMCs from patients with psoriasis. Our findings revealed significant changes in the miRNome of psoriatic blood, in particular miR-223 which

Statement of funding sources

This study was supported by the Ministry of Science, Innovation and Higher education, the Advanced Danish Technology Foundation and the Aage Bang Foundation.

Acknowledgements

We thank Nannie Bangsggard, Department of Dermato-Allergology, Gentofte Hospital for sample acquisition of the whole blood samples, Troels Marstrand, LEO Pharma A/S for valuable discussions during the manuscript preparation and the patients and healthy controls for their participation in the study.

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