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