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类风湿关节炎中的组学方法与治疗反应

-Omic Approaches and Treatment Response in Rheumatoid Arthritis.

作者信息

Madrid-Paredes Adela, Martín Javier, Márquez Ana

机构信息

Department of Clinical Pharmacy, San Cecilio University Hospital, Instituto de Investigación Biosanitaria de Granada (ibs.Granada), 18016 Granada, Spain.

Institute of Parasitology and Biomedicine López-Neyra (IPBLN), Spanish National Research Council (CSIC), 18017 Granada, Spain.

出版信息

Pharmaceutics. 2022 Aug 8;14(8):1648. doi: 10.3390/pharmaceutics14081648.

Abstract

Rheumatoid arthritis (RA) is an inflammatory disorder characterized by an aberrant activation of innate and adaptive immune cells. There are different drugs used for the management of RA, including disease-modifying antirheumatic drugs (DMARDs). However, a significant percentage of RA patients do not initially respond to DMARDs. This interindividual variation in drug response is caused by a combination of environmental, genetic and epigenetic factors. In this sense, recent -omic studies have evidenced different molecular signatures involved in this lack of response. The aim of this review is to provide an updated overview of the potential role of -omic approaches, specifically genomics, epigenomics, transcriptomics, and proteomics, to identify molecular biomarkers to predict the clinical efficacy of therapies currently used in this disorder. Despite the great effort carried out in recent years, to date, there are still no validated biomarkers of response to the drugs currently used in RA. -Omic studies have evidenced significant differences in the molecular profiles associated with treatment response for the different drugs used in RA as well as for different cell types. Therefore, global and cell type-specific -omic studies analyzing response to the complete therapeutical arsenal used in RA, including less studied therapies, such as sarilumab and JAK inhibitors, are greatly needed.

摘要

类风湿性关节炎(RA)是一种炎症性疾病,其特征是先天性和适应性免疫细胞异常激活。有多种药物用于治疗RA,包括改善病情抗风湿药(DMARDs)。然而,相当一部分RA患者最初对DMARDs没有反应。这种个体间药物反应差异是由环境、遗传和表观遗传因素共同导致的。从这个意义上说,最近的组学研究已经证明了与这种无反应相关的不同分子特征。这篇综述的目的是提供一个最新的概述,介绍组学方法,特别是基因组学、表观基因组学、转录组学和蛋白质组学在识别分子生物标志物以预测目前用于该疾病的治疗方法的临床疗效方面的潜在作用。尽管近年来付出了巨大努力,但迄今为止,仍没有针对目前用于RA的药物的经过验证的反应生物标志物。组学研究已经证明,与RA中使用的不同药物以及不同细胞类型的治疗反应相关的分子谱存在显著差异。因此,非常需要进行全面的和细胞类型特异性的组学研究,以分析对RA中使用的完整治疗药物库(包括研究较少的疗法,如托珠单抗和JAK抑制剂)的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c16e/9412998/2db66a8d4e8a/pharmaceutics-14-01648-g001.jpg

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