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分析乌司奴单抗治疗寻常型银屑病患者的临床应答和 TNF-α 及其 TNFR1 和 TNFR2 受体表达的变化。

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.

机构信息

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

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

出版信息

Adv Clin Exp Med. 2020 Feb;29(2):235-241. doi: 10.17219/acem/112607.

DOI:10.17219/acem/112607
PMID:32125100
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.

CONCLUSIONS

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.

摘要

背景

乌司奴单抗是一种单克隆抗体,能够与白细胞介素 12(IL-12)和白细胞介素 23(IL-23)的共同亚单位 p40 结合,从而阻止 JAK-STAT 信号通路的激活。

目的

本研究旨在评估抗 IL-12/23 药物治疗寻常型银屑病患者的疗效,根据疾病临床进展指标(银屑病面积和严重程度指数(PASI)、皮肤病生活质量指数(DLQI)和体表面积(BSA)),并确定肿瘤坏死因子 α(TNF-α)、肿瘤坏死因子受体 1(TNFR1)和 TNFR2 表达谱变化作为分子标志物来预测乌司奴单抗治疗反应的可能性。

材料与方法

研究组由 14 名患者(10 名男性和 4 名女性,年龄 49.3±10.2 岁)组成,这些患者被诊断为寻常型银屑病,接受乌司奴单抗治疗。根据所选的 3 个治疗阶段,将该组分为亚组。对照组由 20 名健康志愿者(11 名男性和 9 名女性,年龄 46±10 岁)组成。120 周的观察期包括对患者进行临床评估(PASI、BSA 和 DLQI),评估方案如下:0-4-12 周观察期。采用定量逆转录聚合酶链反应(RT-qPCR)法分析 TNF-α、TNFR1 和 TNFR2 表达谱的分子变化,使用患者的全血进行分析。采用 STATISTICA v.12.0 PL(StatSoft Inc.,Tulsa,USA)进行统计分析,统计显著性水平为 p<0.05。

结果

在抗 IL-12/23 治疗期间,逐渐降低了 PASI、BSA 和 DLQI 值。与对照组相比,分析组的 TNF-α转录活性水平升高。还表明了临床和分子参数之间的相关性。

结论

乌司奴单抗是治疗寻常型银屑病的一种有效且安全的药物治疗方法。当重新对患者进行治疗分类时,我们未观察到治疗效果降低的情况。肿瘤坏死因子 α、TNFR1 和 TNFR2 可作为药物分子反应的补充标志物。

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