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Multidrug resistance protein-1 expression, function and polymorphisms in patients with rheumatoid arthritis not

Shiva Prasad1, Deepak Tripathi, Mohit K Rai

  • 1Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

International Journal of Rheumatic Diseases
|April 17, 2014
PubMed
Abstract

Insights

Persistent expression of MDR-1 protein in rheumatoid arthritis (RA) patients indicates poor response to methotrexate (MTX) therapy. Monitoring MDR-1 levels may help tailor RA treatment strategies.

Area of Science:

  • Immunology
  • Pharmacology
  • Rheumatology

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease.
  • Methotrexate (MTX) is a common disease-modifying antirheumatic drug (DMARD).
  • MDR-1 protein (P-glycoprotein) influences drug transport and response.

Purpose of the Study:

  • To investigate MDR-1 protein expression, function, and polymorphism in RA patients treated with MTX.
  • To determine the relationship between MDR-1 and therapeutic response to MTX.
  • To identify potential biomarkers for MTX unresponsiveness.

Main Methods:

  • Flow cytometry was used to assess MDR-1 expression and function in peripheral blood lymphocytes of RA patients before and after 4 months of MTX therapy.
  • MDR-1 function was evaluated by Rhodamine efflux assay.
  • Patients were classified as responders or non-responders based on changes in disease activity score (DAS28).
  • Analysis of three single nucleotide polymorphisms (SNPs) in the MDR-1 gene.

Main Results:

  • A significant reduction in MDR-1 expression and function was observed in MTX responders compared to baseline.
  • Non-responders showed increased or unchanged MDR-1 expression and function after MTX treatment.
  • No significant difference in MDR-1 expression or function was found between responders and non-responders at baseline.
  • MTX unresponsiveness was not associated with the studied MDR-1 gene polymorphisms.

Conclusions:

  • Persistent MDR-1 expression and function identify RA patients unlikely to respond to MTX.
  • Early identification of high MDR-1 levels could guide therapeutic adjustments in RA management.
  • MDR-1 may serve as a predictive biomarker for MTX efficacy in RA.
Keywords:
Rhodamine dye exclusionfailuremethotrexatemultidrug resistance protein-1peripheral blood lymphocytesrheumatoid arthritis

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