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俄罗斯类风湿关节炎患者中与奥洛珠单抗治疗相关的遗传和临床因素

Genetic and Clinical Factors Associated with Olokizumab Treatment in Russian Patients with Rheumatoid Arthritis.

作者信息

Mikhaylenko Dmitry S, Kuznetsova Ekaterina B, Musatova Viktoria V, Bure Irina V, Deryagina Tatiana A, Alekseeva Ekaterina A, Tarasov Vadim V, Zamyatnin Andrey A, Nemtsova Marina V

机构信息

Laboratory of Medical Genetics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.

Laboratory of Epigenetics, Research Centre for Medical Genetics, 115522 Moscow, Russia.

出版信息

J Pers Med. 2022 Apr 15;12(4):641. doi: 10.3390/jpm12040641.

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease and its treatment is an urgent problem of rheumatology. Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 and is one of the few promising drugs for RA therapy. One-hundred-and-twenty-five DNA samples from Russian patients with RA, treated with olokizumab, were genotyped with an NGS panel containing 60 single nucleotide polymorphisms (SNPs) and the whole coding sequences of , , , , , , and ; and by RT-PCR for HLA-DRB1 and HLA-B. Associations of polymorphic variants with olokizumab efficacy according to the scores ACR20, ACR50, and DAS28-CRP were determined. We analyzed the obtained data by using logistic regression, ROC curves, and multivariate ANOVA. A high predictive value of the response to olokizumab therapy at 24 weeks was found for the combination of HLA-DRB104 and HLA-B27 alleles with SNPs located in non-HLA genes (, , , , , , and ), and clinical characteristics (age, RA duration, and intensity) according to ACR20. Thus, the comprehensive assessment of polymorphic variants of HLA and non-HLA genes considering population characteristics in combination with clinical parameters allows for the elaboration of an RA prognostic panel.

摘要

类风湿关节炎(RA)是一种慢性全身性炎症性疾病,其治疗是风湿病学的一个紧迫问题。奥洛珠单抗(OKZ)是一种新型的靶向白细胞介素-6的人源化单克隆抗体,是少数有前景的用于RA治疗的药物之一。对125例接受奥洛珠单抗治疗的俄罗斯RA患者的DNA样本进行基因分型,使用包含60个单核苷酸多态性(SNP)以及、、、、、和的完整编码序列的二代测序(NGS)面板;并通过逆转录聚合酶链反应(RT-PCR)检测HLA-DRB1和HLA-B。根据美国风湿病学会20%改善标准(ACR20)、美国风湿病学会50%改善标准(ACR50)和28个关节疾病活动评分(DAS28-CRP)确定多态性变体与奥洛珠单抗疗效的关联。我们使用逻辑回归、ROC曲线和多因素方差分析对获得的数据进行分析。发现HLA-DRB104和HLA-B27等位基因与位于非HLA基因(、、、、、和)中的SNP以及根据ACR20的临床特征(年龄、RA病程和疾病强度)相结合,对奥洛珠单抗治疗24周时的反应具有较高的预测价值。因此,结合人群特征并考虑临床参数,对HLA和非HLA基因的多态性变体进行综合评估,有助于制定RA预后评估指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c9e/9024465/461020e44a70/jpm-12-00641-g001.jpg

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