Wysocki Tomasz, Paradowska-Gorycka Agnieszka
Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637 Warsaw, Poland.
Int J Mol Sci. 2022 Feb 21;23(4):2366. doi: 10.3390/ijms23042366.
Rheumatoid arthritis (RA) is the most commonly occurring chronic inflammatory arthritis, the exact mechanism of which is not fully understood. Tumor Necrosis Factor (TNF)-targeting drugs has been shown to exert high effectiveness for RA, which indicates the key importance of this cytokine in this disease. Nevertheless, the response to TNF inhibitors varies, and approximately one third of RA patients are non-responders, which is explained by the influence of genetic factors. Knowledge in the field of pharmacogenomics of anti-TNF drugs is growing, but has not been applied in the clinical practice so far. Different genome-wide association studies identified a few single nucleotide polymorphisms associated with anti-TNF treatment response, which largely map genes involved in T cell function. Studies of the gene expression profile of RA patients have also indicated specific gene signatures that may be useful to develop novel prognostic tools. In this article, we discuss the significance of TNF in RA and present the current knowledge in pharmacogenomics related to anti-TNF treatment response.
类风湿关节炎(RA)是最常见的慢性炎症性关节炎,其确切机制尚未完全明确。已证明肿瘤坏死因子(TNF)靶向药物对RA具有高效性,这表明该细胞因子在这种疾病中至关重要。然而,对TNF抑制剂的反应存在差异,约三分之一的RA患者无反应,这可由遗传因素的影响来解释。抗TNF药物的药物基因组学领域的知识不断增长,但迄今为止尚未应用于临床实践。不同的全基因组关联研究确定了一些与抗TNF治疗反应相关的单核苷酸多态性,这些多态性大多定位在参与T细胞功能的基因上。对RA患者基因表达谱的研究也表明了特定的基因特征,这些特征可能有助于开发新的预后工具。在本文中,我们讨论了TNF在RA中的意义,并介绍了与抗TNF治疗反应相关的药物基因组学的当前知识。