Rheumatoid Factor Positivity Is Associated with Increased Joint Destruction and Upregulation of Matrix Metalloproteinase 9 and Cathepsin K Gene Expression in the Peripheral Blood in Rheumatoid Arthritic Patients Treated with Methotrexate
We evaluated changes in gene expression of mTOR, p21, caspase-3, ULK1, TNFα, matrix metalloproteinase (MMP)-9, and cathepsin K in the whole blood of rheumatoid arthritic (RA) patients treated with methotrexate (MTX) in relation to their rheumatoid factor status, clinical, immunological, and radiological parameters, and therapeutic response after a 24-month follow-up. The study group consisted of 35 control subjects and 33 RA patients without previous history of MTX treatment. Gene expression was measured using real-time RT-PCR. Decreased disease activity in patients at the end of the study was associated with significant downregulation of TNFα expression. Downregulation of mTOR was observed in seronegative patients, while no significant changes in the expression of p21, ULK1, or caspase-3 were noted in any RA patients at the end of the study. The increase in erosion numbers observed in the seropositive patients at the end of the follow-up was accompanied by upregulation of MMP-9 and cathepsin K, while seronegative patients demonstrated an absence of significant changes in MMP-9 and cathepsin K expression and no increase in the erosion score. Our results suggest that increased expression of MMP-9 and cathepsin K genes in the peripheral blood might indicate higher bone tissue destruction activity in RA patients treated with methotrexate. The clinical study registration number is 0120.0810610. 1. Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia, mononuclear cell infiltration, bone erosion, and joint destruction. Early diagnosis and immediate aggressive treatment are required for the amelioration of progressive joint damage and patient disability [1, 2]. Methotrexate (MTX) is the most conventional disease-modifying antirheumatic drug (DMARD) for RA, with the best efficacy and the fewest adverse effects [3, 4]. However, only approximately 30% of patients respond to MTX treatment [5, 6]. The identification of patients who are less responsive to MTX could avoid delays in adjusting their treatment and prevent future irreversible joint damage [7]. Rheumatoid factor (RF) is a part of the 2010 American College of Rheumatology (ACR) classification criteria for RA [8]. RF is an autoantibody directed against the Fc portion of IgG and is associated with disease persistence and progressive joint destruction [9–11]. However, the data related to RF status in treatment response to MTX is inconsistent, as some studies reported no association between RF positivity and treatment efficacy [12–21], while others
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