Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy.

Autor: Tchetina EV; Immunology & Molecular Biology Laboratory, Nasonova Research Institute of Rheumatology, Moscow, Russia., Demidova NV; Early Rheumatoid Arthritis Department, Nasonova Research Institute of Rheumatology, Moscow, Russia., Markova GA; Immunology & Molecular Biology Laboratory, Nasonova Research Institute of Rheumatology, Moscow, Russia., Taskina EA; Osteoarthritis Laboratory, Nasonova Research Institute of Rheumatology, Moscow, Russia., Glukhova SI; Statistics Department, Nasonova Research Institute of Rheumatology, Moscow, Russia., Karateev DE; Early Rheumatoid Arthritis Department, Nasonova Research Institute of Rheumatology, Moscow, Russia.
Jazyk: angličtina
Zdroj: International journal of rheumatic diseases [Int J Rheum Dis] 2017 Oct; Vol. 20 (10), pp. 1468-1480. Date of Electronic Publication: 2017 Jul 25.
DOI: 10.1111/1756-185X.13131
Abstrakt: Objective: To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment.
Methods: Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response.
Results: Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values.
Conclusions: Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy.
(© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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