Evaluation of Tyrosine Kinase-2 (TYK2) signaling pathway gene expression and the presence of the single-nucleotide polymorphism rs12720356 in the peripheral blood of patients with severe psoriasis and loss of systemic treatment response

IF 3.6 4区医学 Q2 DERMATOLOGY

Anais brasileiros de dermatologia Pub Date : 2025-08-04 DOI:10.1016/j.abd.2025.501165

Paola Borges Eckstein Canabrava , Roll Stanley Beauge , Samir de Figueiredo Azouz , Renata Velozo Timbó , Luciana Pereira Freire Martins , Bruna Côrtes Rodrigues , Naiara Daris dos Santos , Marcella Palhano Medeiros , Andréa Monteiro de Araújo , Agenor de Castro Moreira dos Santos Júnior , Carla Nunes de Araújo , Otávio de Toledo Nóbrega , Patrícia Shu Kurizky , Licia Maria Henrique da Mota , Ciro Martins Gomes

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引用次数: 0

Abstract

Background

RNA sequencing-based studies have identified the transcription processes that contribute to psoriasis development, but the associations of these processes with specific phenotypes need further investigation.

Objective

The authors aimed to determine the associations of specific Peripheral Blood Mononuclear Cell (PBMC) endotypic profiles with loss of treatment response in psoriasis patients.

Methods

A Psoriasis Area and Severity Index (PASI) > 10 was the main outcome. The gene expression of Tyrosine Kinase-2 (TYK), Interleukin (IL)-12A, IL-12B, IL-23A, IL-23 Receptor (IL-23R), IL-6, IL-6R,IL-17A and Tumor Necrosis Factor (TNF) in PBMCs was quantified as possible risk factors. Single-Nucleotide Polymorphisms (SNP) were screened using a genotyping technique. Hierarchical clustering of the gene expression results was performed.

Results

The authors included 178 psoriasis patients. TYK2 was upregulated in the PBMCs of patients with a PASI score > 10, but its distribution was widely variable. A cluster of 19 patients exhibited upregulated expression of most TYK2-dependent mediators and increased PASI (p = 0.021) and Dermatology Life Quality Index (DLQI) scores (p = 0.034). Three patients harbored the TYK2I684S variant.

Study limitations

The utility of using single markers for psoriasis diagnosis is limited due to the wide variability of results, but the utility of the simultaneous evaluation of a set of markers has promise.

Conclusions

The present study suggests an association between multiple TYK2 pathway markers and loss of systemic treatment response.

查看原文本刊更多论文

重度银屑病患者外周血酪氨酸激酶-2 （TYK2）信号通路基因表达及单核苷酸多态性rs12720356的存在评估及全身治疗反应丧失

背景：基于RNA测序的研究已经确定了促进银屑病发展的转录过程，但这些过程与特定表型的关联需要进一步研究。目的：作者旨在确定特异性外周血单个核细胞（PBMC）内分型与银屑病患者治疗反应丧失的关系。方法：以银屑病面积及严重程度指数（PASI）为主要观察指标。将酪氨酸激酶-2 （TYK）、白细胞介素(IL)-12A、IL- 12b、IL- 23a、IL-23受体（IL- 23r）、IL-6、IL- 6r、IL- 17a和肿瘤坏死因子（TNF）的基因表达作为可能的危险因素进行量化。采用基因分型技术筛选单核苷酸多态性（SNP）。对基因表达结果进行分层聚类。结果：纳入178例银屑病患者。TYK2在PASI评分为bb10的患者的PBMCs中上调，但其分布差异很大。19例患者表现出大多数tyk2依赖性介质的表达上调，PASI （p = 0.021）和皮肤生活质量指数（DLQI）评分升高（p = 0.034）。三名患者携带TYK2I684S变异。研究局限性：由于结果的广泛可变性，使用单一标记物诊断牛皮癣的效用受到限制，但同时评估一组标记物的效用是有希望的。结论：目前的研究表明，多种TYK2通路标志物与全身治疗反应的丧失之间存在关联。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anais brasileiros de dermatologia DERMATOLOGY-

CiteScore

2.40

自引率

0.00%

发文量

184

审稿时长

32 days

期刊介绍： The journal is published bimonthly and is devoted to the dissemination of original, unpublished technical-scientific study, resulting from research or reviews of dermatological topics and related matters. Exchanges with other publications may be accepted.