| Autor: |
Mikhaylenko DS; 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., Kuznetsova EB; Laboratory of Medical Genetics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia., Musatova VV; Laboratory of Epigenetics, Research Centre for Medical Genetics, 115522 Moscow, Russia., Bure IV; Laboratory of Medical Genetics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia., Deryagina TA; Laboratory of Epigenetics, Research Centre for Medical Genetics, 115522 Moscow, Russia., Alekseeva EA; 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., Tarasov VV; Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia., Zamyatnin AA Jr; Laboratory of Medical Genetics, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Department of Biotechnology, Sirius University of Science and Technology, 1 Olympic Ave, 354340 Sochi, Russia.; Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7X, UK., Nemtsova MV; 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. |
| Abstrakt: |
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 IL6 , IL6R , TNFRSF1A , CTLA4 , IL10 , IL23R , and PADI4 ; 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-DRB1*04 and HLA-B*27 alleles with SNPs located in non-HLA genes ( IL1B , IL17A , PADI4 , DHODH , GLCCI1 , IL23R , and TNFAIP3 ), 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. |
