title: 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.
abstract: We evaluated changes in gene expression of mTOR, p21, caspase-3, ULK1, TNF α , 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 TNF α 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.
authors.affiliation: Clinical Immunology Department, Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Kashirskoye Shosse 34A, Moscow 115522, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Tchetina
authors.affiliation: Early Rheumatoid Arthritis Department, Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Demidova
authors.affiliation: Early Rheumatoid Arthritis Department, Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia.
authors.forename: Dmitry E
authors.initials: DE
authors.lastname: Karateev
authors.affiliation: Vascular Pathology Department, Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia.
authors.forename: Eugeny L
authors.initials: EL
authors.lastname: Nasonov