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

Elena V Tchetina; Natalia V Demidova; Dmitry E Karateev; Eugeny L Nasonov

doi:10.1155/2013/457876

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

Int J Rheumatol. 2013:2013:457876. doi: 10.1155/2013/457876. Epub 2013 Nov 14.

Authors

Elena V Tchetina¹, Natalia V Demidova², Dmitry E Karateev², Eugeny L Nasonov³

Affiliations

¹ Clinical Immunology Department, Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Kashirskoye Shosse 34A, Moscow 115522, Russia.
² Early Rheumatoid Arthritis Department, Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia.
³ Vascular Pathology Department, Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia.

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.