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

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.

International journal of rheumatology

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

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.

PMID: 24348567 PMCID: PMC3848347 DOI: 10.1155/2013/457876

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.

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