Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 2, February, p. 235–241

doi: 10.17219/acem/112607

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Analysis of the clinical response and changes in the expression of TNF-α and its TNFR1 and TNFR2 receptors in patients with psoriasis vulgaris treated with ustekinumab

Dominika Ligia Wcisło-Dziadecka1,A,B,C,D,E,F, Beniamin Grabarek2,3,4,C,D, Celina Kruszniewska-Rajs2,C, Joanna Magdalena Gola2,B,C,E, Klaudia Simka5,C, Urszula Mazurek6,D,E,F

1 Department of Cosmetology, School of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Poland

2 Department of Molecular Biology, School of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Poland

3 Maria Sklodowska-Curie National Research Institute of Oncology Krakow Branch, Poland

4 Department of Histology, Cytophysiology and Embryology in Zabrze, Silesian University of Technology, Faculty of Medicine, Katowice, Poland

5 Department of Internal Medicine, School of Health Sciences in Bytom, Medical University of Silesia in Katowice, Poland

6 Józef Tyszkiewicz Higher School in Bielsko-Biała, Poland

Abstract

Background. Ustekinumab is a monoclonal antibody that shows the ability to bind to subunit p40, common for interleukin 12 (IL-12) and IL-23, which prevents the activation of the JAK STAT signaling pathway.
Objectives. The objective of the study was to evaluate the efficacy of therapy that uses anti-IL-12/23 medicine in patients with psoriasis vulgaris, based on the disease clinical progression indices (Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and Body Surface Area (BSA)) and to determine the possibilities of using changes in the expression profiles of tumor necrosis factor α (TNF-α), tumor necrosis factor receptor (TNFR1) and TNFR2 as molecular markers showing the response to ustekinumab therapy.
Material and Methods. The group under study was composed of 14 patients (10 men and 4 women, aged 49.3 ±10.2 years) with diagnosed psoriasis vulgaris, treated with ustekinumab. The group was divided into subgroups because of the selected 3 stages of therapy. The control group consisted of 20 healthy volunteers (11 men and 9 women, aged 46 ±10 years). The 120-week long observation involved a clinical assessment of the patients (PASI, BSA and DLQI), based on the following scheme: 0–4–12 weeks of the observation. The analysis of molecular changes in the TNF-α, TNFR1 and TNFR2 expression profiles was performed with the quantitative reverse-transcription polymerase chain reaction (RT-qPCR) method, using the patients’ full blood. The statistical analysis was performed with STATISTICA v. 12.0 PL (StatSoft Inc., Tulsa, USA) with the level of statistical significance p < 0.05.
Results. Gradually reduced PASI, BSA and DLQI values were observed during anti-IL-12/23 therapy. An increased level of the TNF-α transcription activity was observed in the analyzed group when compared to the control. Correlations between the clinical and molecular parameters were also indicated.
Conclusion. Ustekinumab constitutes an efficient and safe form of pharmacotherapy in psoriasis vulgaris. We did not observe any reduced efficacy of the treatment when reclassifying patients for the therapy. Tumor necrosis factor α, TNFR1 and TNFR2 may serve as supplementary markers of molecular response to the medicine.

Key words

psoriasis, TNF-α, molecular marker, anti-IL-12/23 therapy, JAK STAT signaling pathway

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