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接受抗IL-23治疗的银屑病患者循环微小RNA:一项队列研究。

Circulating MicroRNAs in Patients with Psoriasis Treated with Anti-IL-23: A Cohort Study.

作者信息

Diotallevi Federico, Matacchione Giulia, Campanati Anna, Marinelli Busilacchi Elena, Viola Nadia, Pace Ilaria, Fontana Beatrice, Roncarati Roberta, Bonafè Massimiliano, Ferracin Manuela, Sabbatinelli Jacopo, Olivieri Fabiola

机构信息

Dermatological Clinic, Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy.

Clinic of Laboratory and Precision Medicine, IRCCS INRCA, Ancona, Italy.

出版信息

Dermatol Ther (Heidelb). 2025 Jan;15(1):125-140. doi: 10.1007/s13555-024-01331-9. Epub 2025 Jan 12.

Abstract

INTRODUCTION

Psoriasis is characterized by aberrant keratinocyte activity and immune cell infiltration, driven by immune-mediated pathways. MicroRNAs (miRNAs) play crucial roles in regulating these processes, offering insights into disease mechanisms and therapeutic targets.

OBJECTIVES

This study aimed to investigate changes in circulating miRNAs in psoriasis patients undergoing risankizumab therapy, an anti-IL-23 monoclonal antibody, to understand its impact on disease pathogenesis and treatment response.

METHODS

Plasma samples from 12 psoriasis patients were collected before (T0) and after 1 year (T1) of risankizumab treatment and analyzed using small RNA sequencing. Findings were validated in a separate cohort of 23 patients using quantitative real-time PCR (qRT-PCR). T-regulatory cell (Treg) numbers and pro-inflammatory cytokine levels were also assessed.

RESULTS

Significant clinical improvement was observed in all patients after 1 year of treatment, accompanied by increased Treg counts and reduced levels of pro-inflammatory cytokines. Twenty-four miRNAs exhibited differential expression post-treatment; 9 were downregulated and 15 upregulated. Notably, miR-200a-3p showed a significant correlation with baseline Psoriasis Area Severity Index (PASI), indicating its potential as a severity marker. Risankizumab therapy also decreased peripheral blood levels of IL-23, IL-1β, and IL-8.

CONCLUSIONS

This study identifies specific circulating miRNAs, including miR-200a-3p, as potential biomarkers for monitoring treatment responses in psoriasis patients. The findings underscore the therapeutic efficacy of risankizumab in modulating miRNA profiles and immune pathways associated with psoriasis pathogenesis. Overall, these results provide new insights into the mechanisms of risankizumab action and highlight miRNAs as promising candidates for personalized medicine approaches in psoriasis management.

摘要

引言

银屑病的特征是角质形成细胞异常活动和免疫细胞浸润,由免疫介导的途径驱动。微小RNA(miRNA)在调节这些过程中发挥关键作用,为疾病机制和治疗靶点提供了见解。

目的

本研究旨在调查接受司库奇尤单抗治疗(一种抗IL-23单克隆抗体)的银屑病患者循环miRNA的变化,以了解其对疾病发病机制和治疗反应的影响。

方法

收集12例银屑病患者在司库奇尤单抗治疗前(T0)和治疗1年后(T1)的血浆样本,并用小RNA测序进行分析。在另一组23例患者中使用定量实时PCR(qRT-PCR)对结果进行验证。还评估了调节性T细胞(Treg)数量和促炎细胞因子水平。

结果

治疗1年后,所有患者均观察到显著的临床改善,同时Treg计数增加,促炎细胞因子水平降低。24种miRNA在治疗后表现出差异表达;9种下调,15种上调。值得注意的是,miR-200a-3p与基线银屑病面积和严重程度指数(PASI)显著相关,表明其作为严重程度标志物的潜力。司库奇尤单抗治疗还降低了外周血中IL-23、IL-1β和IL-8的水平。

结论

本研究确定了特定循环miRNA,包括miR-200a-3p,作为监测银屑病患者治疗反应的潜在生物标志物。这些发现强调了司库奇尤单抗在调节与银屑病发病机制相关的miRNA谱和免疫途径方面的治疗效果。总体而言,这些结果为司库奇尤单抗的作用机制提供了新见解,并突出了miRNA作为银屑病管理中个性化医疗方法的有前景候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a82/11785893/0279f2da1141/13555_2024_1331_Fig1_HTML.jpg

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