Impact of FCGR2A R131H, FCGR3A F158V and FCGR3B NA1/NA2 polymorphisms on response to Fc-containing TNF inhibitors in Tunisian rheumatoid arthritis patients.

Q2 Pharmacology, Toxicology and Pharmaceutics

Drug metabolism and personalized therapy Pub Date : 2023-06-01 DOI:10.1515/dmpt-2022-0176

Mahmoud Ines, Moalla Myriam, Ben Tekaya Aicha, Bouden Selma, Rouached Leila, Tekaya Rawdha, Saidane Olfa, Gorji Yousr, Elleuch Mohamed, Laatar Ahmed, Hamdi Wafa, Abdelmoula Leila, Sfar Imen

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引用次数: 1

Abstract

Objectives: Single nucleotid polymorphisms (SNPs) of Fc-gamma receptors (FcgRs), by inducing a variation of their affinity to the Fc-region of immunoglobulins, might influence the efficacy of Fc-containing biologics prescribed in rheumatoid arthritis (RA). Our aim was to investigate associations of FCGR2A, FCGR3A and FCGR3B SNPs with TNF-inhibitors (TNFi)' response in Tunisian RA patients.

Methods: A cross-sectional, observational and analytic multicentric cohort study was conducted in a group of 47 Tunisian RA patients treated with (etanercept [ETA], adalimumab [ADL] and infliximab [IFX]). Treatment outcome was evaluated after 6 months. R131H-FCGR2A, F158V-FCGR3A and NA1/NA2-FCGR3B SNPs were genotyped.

Results: The analytic study including all types of TNFi showed that FCGR3A-F/F low-affinity receptor was associated with a greater decrease of DAS28, while FCGR3B-NA1/NA1 high-affinity receptor was associated with a lower decrease of DAS28 in ADL group. Furthermore, both of high affinity receptors FCGR3B-NA1/NA1 and FCGR3A-V/V were more prevalent in non-responders to ADL, according to EULAR criteria.

Conclusions: Identifying reliable biomarkers of response to biologics in RA is necessary to improve responsiveness, preserve joints' functions and structure, and reduce treatment's cost. Our study showed that FCGR3A and FCGR3B polymorphisms might have an impact on TNFis' response in RA Tunisian patients since bad response was more frequent in homozygous carriers of high affinity alleles FCGR3A-V and FCGR3B-NA1.

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FCGR2A R131H、FCGR3A F158V和FCGR3B NA1/NA2多态性对突尼斯类风湿性关节炎患者含fc TNF抑制剂应答的影响

目的:fc - γ受体(fcgr)的单核苷酸多态性(snp)，通过诱导其对免疫球蛋白fc区亲和力的变化，可能影响类风湿关节炎(RA)含fc生物制剂的疗效。我们的目的是研究突尼斯类风湿性关节炎患者中FCGR2A、FCGR3A和FCGR3B snp与tnf -抑制剂(TNFi)反应的关系。方法:对47例突尼斯RA患者(依他那西普[ETA]、阿达木单抗[ADL]和英夫利昔单抗[IFX])进行了横断、观察和分析性多中心队列研究。6个月后评估治疗效果。对R131H-FCGR2A、F158V-FCGR3A和NA1/NA2-FCGR3B snp进行基因分型。结果:包括所有TNFi类型的分析研究显示，在ADL组中，FCGR3A-F/F低亲和受体与DAS28的下降幅度较大，而fcgr3a -NA1/NA1高亲和受体与DAS28的下降幅度较小。此外，根据EULAR标准，高亲和受体FCGR3B-NA1/NA1和FCGR3A-V/V在ADL无应答者中更为普遍。结论:确定可靠的RA对生物制剂反应的生物标志物对于提高RA的反应性、保护关节功能和结构以及降低治疗成本是必要的。我们的研究表明，FCGR3A和FCGR3B多态性可能对突尼斯RA患者的TNFis反应有影响，因为高亲和力等位基因FCGR3A- v和FCGR3B- na1的纯合携带者更容易出现不良反应。

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

Drug metabolism and personalized therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

2.30

自引率

0.00%

发文量

期刊介绍： Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.