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Down regulation of multidrug resistance protein-1 expression in patients with early rheumatoid arthritis exposed to methotrexate as a first disease-modifying antirheumatic drug
  1. S L Hider1,
  2. A Owen2,
  3. R Hartkoorn2,
  4. S Khoo2,
  5. D Back2,
  6. A J Silman1,
  7. I N Bruce1
  1. 1arc Epidemiology Unit, University of Manchester, Manchester, UK
  2. 2HIV Pharmacology Group, University of Liverpool, Liverpool, UK
  1. Correspondence to:
    S L Hider
    arc Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK; sam.hider{at}manchester.ac.uk

Abstract

Background: Methotrexate (MTX) is the current gold standard conventional disease-modifying antirheumatic drug (DMARD) and is effluxed from cells by several transmembrane proteins, including multidrug resistance protein-1 (MRP1). It is hypothesised that the overexpression of these proteins may mediate reduced efficacy of MTX. To date, it is unclear how expression of these proteins changes over time or after exposure to drugs.

Aims: To compare MRP1 expression in newly diagnosed patients with DMARD-naive rheumatoid arthritis with that in healthy controls and to investigate how MRP1 expression changed after exposure to MTX.

Methods: 18 newly diagnosed patients with DMARD-naive rheumatoid arthritis and 14 healthy controls were recruited. Peripheral blood mononuclear cell counts were taken at baseline and after 6 months’ treatment with MTX. Cells were separated by density gradient centrifugation and MRP1 expression was measured using the QCRL-1 monoclonal antibody.

Results: MRP1 expression in patients did not seem to be up regulated compared with that in healthy controls. In patients who were positive for MRP1 at baseline (61%), treatment with MTX and folic acid led to a marked down regulation of MRP1 expression at 6 months.

Conclusion: In patients with rheumatoid arthritis expressing MRP1, treatment with MTX and folic acid led to down regulation of MRP1 expression. Further studies are required to determine the mechanism behind this observation and whether MRP1 expression mediates altered efficacy to MTX.

  • DAS28, Disease Activity Score 28
  • DMARD, disease-modifying antirheumatic drug, IQR, interquartile range
  • MRP, multidrug resistance protein
  • MTX, methotrexate
  • P-gp, P-glycoprotein
  • PBMCs, peripheral blood mononuclear cells
  • RFC, reduced folate carrier

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Footnotes

  • Competing interests: None.

  • Published Online First 27 February 2006

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