Association of polymorphisms of HLA-DRB1 and TNF-308 G/A with radiographic joint damage in patients with early rheumatoid arthritis with high inflammatory activity, treated according to the principle of "Treat to target" (REMARKA study).
| Autor: | Guseva IA; Federal State Budgetary Scientific Institution «Research Institute of Rheumatology named after V.A. Nasonova», Moscow, Russia., Smirnov AV; Federal State Budgetary Scientific Institution «Research Institute of Rheumatology named after V.A. Nasonova», Moscow, Russia., Demidova NV; Federal State Budgetary Scientific Institution «Research Institute of Rheumatology named after V.A. Nasonova», Moscow, Russia., Krylov MY; Federal State Budgetary Scientific Institution «Research Institute of Rheumatology named after V.A. Nasonova», Moscow, Russia., Avdeeva AS; Federal State Budgetary Scientific Institution «Research Institute of Rheumatology named after V.A. Nasonova», Moscow, Russia., Samarkina EY; Federal State Budgetary Scientific Institution «Research Institute of Rheumatology named after V.A. Nasonova», Moscow, Russia., Luchikhina EL; Moscow Regional Research and Clinical Institute (MONIKI), Moscow, Russia., Karateev DE; Moscow Regional Research and Clinical Institute (MONIKI), Moscow, Russia., Abramov DD; National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia., Nasonov EL; Federal State Budgetary Scientific Institution «Research Institute of Rheumatology named after V.A. Nasonova», Moscow, Russia.; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia. |
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| Jazyk: | angličtina |
| Zdroj: | Terapevticheskii arkhiv [Ter Arkh] 2018 May 11; Vol. 90 (5), pp. 38-43. |
| DOI: | 10.26442/terarkh201890538-43 |
| Abstrakt: | Aim: To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. Materials and Methods: The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of *04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1*01, *04:01, *04:04, *04:05, *04:08, *10 alleles were categorized as SE+ (Shared Epitope) alleles. Results: As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (р<0,005, and р<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (∆) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1*(SE) genotypes: the carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (р<0,028, р<0,019, р<0,035 respectively). Conclusion: Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy. |
| Databáze: | MEDLINE |
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