Rheumatoid Factor Positivity Is Associated with Increased Joint Destruction and Upregulation ofMatrix Metalloproteinase 9andCathepsin KGene Expression in the Peripheral Blood in Rheumatoid Arthritic Patients Treated with Methotrexate

Abstract

We evaluated changes in gene expression ofmTOR,p21,caspase-3,ULK1,TNFα, matrix metalloproteinase(MMP)-9, andcathepsin Kin 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 ofTNFαexpression. Downregulation ofmTORwas observed in seronegative patients, while no significant changes in the expression ofp21,ULK1, orcaspase-3were 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 ofMMP-9andcathepsin K, while seronegative patients demonstrated an absence of significant changes inMMP-9andcathepsin Kexpression and no increase in the erosion score. Our results suggest that increased expression ofMMP-9andcathepsin Kgenes 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.