Changes in the level of serum microRNAs in patients with psoriasis after antitumour necrosis factor-α therapy

Authors

  • A. Pivarcsi,

    Corresponding author
    • Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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  • F. Meisgen,

    1. Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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  • N. Xu,

    1. Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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  • M. Ståhle,

    1. Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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  • E. Sonkoly

    1. Molecular Dermatology Research Group, Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
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  • Funding sources This work was supported by the Swedish Research Council (Vetenskapsrådet), the Swedish Psoriasis Association (Psoriasisförbundet), the National Psoriasis Foundation of the U.S.A., the Welander and Finsens Foundation, Center of Excellence for Research on Inflammation and Cardiovascular disease (CERIC), Karolinska Institutet, and the Stockholm County Council.
  • Conflicts of interest The authors state no conflict of interest.

Correspondence

Andor Pivarcsi.

E-mail: andor.pivarcsi@ki.se

Summary

Background

MicroRNAs (miRNAs) are endogenous, nonprotein-coding, regulatory RNAs with important roles in health and disease. miRNAs are present in the circulation in a stable form and their levels are altered in diseases.

Objectives

To determine whether antitumour necrosis factor (TNF)-α therapy affects serum miRNA levels in patients with psoriasis.

Methods

Serum samples were obtained from healthy donors and from patients with chronic plaque psoriasis before and 12 weeks after the initiation of treatment with the TNF-inhibitor etanercept or methotrexate. miRNA expression profiling was utilized to identify miRNAs with altered serum level in psoriasis, as well as anti-TNF-α-regulated miRNAs in patients' sera. The expression of five miRNAs regulated by etanercept was measured by quantitative polymerase chain reaction (qPCR) in sera from patients and controls.

Results

Etanercept significantly suppressed a panel of 38 miRNAs, which were found to be predominantly immune-cell derived and which have been implicated in inflammation and autoimmunity. Validation by qPCR showed that serum levels of miR-106b, miR-26b, miR-142-3p, miR-223 and miR-126 were significantly downregulated by etanercept in responders (Psoriasis Area and Severity Index change > 50%). By contrast, methotrexate did not significantly affect the levels of these miRNAs. Serum levels of these miRNAs were not upregulated in patients with psoriasis compared with healthy controls. The level of four circulating miRNAs was significantly different (increased: miR-128a; decreased: let-7d, miR-142-3p, miR-181a) in psoriasis and healthy serum.

Conclusions

The level of circulating miRNAs is altered in psoriasis. Anti-TNF-α therapy has a profound effect on the serum level of miRNAs; however, these are not related to disease severity. Our results suggest that changes in the miRNA level may reflect a previously unknown effect of anti-TNF-α therapy. Our results suggest the involvement of miRNAs in pathways affected by anti-TNF-α therapy and warrant further investigation of serum miRNAs as potential biomarkers for therapy response in psoriasis.

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