MDR-1 and MRP-1 activity in peripheral blood leukocytes of rheumatoid arthritis patients

Tamás Micsik, A. Lőrincz, János Gál, Richard Schwab, I. Peták

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Rheumatoid Arthritis is a chronic disease leading to decreased quality of life with a rather variable response rate to Disease Modifying Anti Rheumatic Drugs. Methotrexate (MTX) is the gold standard therapy in Rheumatoid Arthritis. The Multidrug resistance Related Protein and Multi Drug Resistance protein 1, also called P-glycoprotein-170 transporters can alter the intracellular concentration of different drugs. Methotrexate is an MRP1 substrate and thus the functional activity of MRP1 might have a clinical impact on the efficiency of the Methotrexate-therapy in Rheumatoid Arthritis. Methods: We have compared the functional Multidrug Activity Factors (MAF) of the MDR1 and MRP1 transporters of Peripheral Blood Leukocytes of 59 Rheumatoid Arthritis patients with various response rate to MTX-therapy (MTX-responder, MTX-resistant and MTX-intolerant RA-groups) and 47 non-RA controls in six different leukocyte subpopulations (neutrophil leukocytes, monocytes, lymphocytes, CD4+, CD8+ and CD19+ cells). There was a decreased MAF of RA patients compared to non- Rheumatoid Arthritis patients and healthy controls in the leukocyte subpopulations. There was a significant difference between the MAF values of the MTX-responder and MTX intolerant groups. But we have not found significant differences between the MAF values of the MTX-responder and MTX-resistant Rheumatoid Arthritis -groups. Results: Our results suggest that MDR1 and MRP1 functional activity does not seem to affect the response rate to MTX-therapy of Rheumatoid Arthritis-patients, but it might be useful in predicting MTX-side effects. We have demonstrated the decreased functional MDR-activity on almost 60 Rheumatoid Arthritis patients, which can be interpreted as a sign of the immune-suppressive effect of the MTX-treatment.

Original languageEnglish
Article number216
JournalDiagnostic Pathology
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 30 2015

Fingerprint

Methotrexate
Rheumatoid Arthritis
Leukocytes
P-Glycoproteins
Therapeutics
Antirheumatic Agents
Multiple Drug Resistance
P-Glycoprotein
Monocytes
Neutrophils
Chronic Disease
Quality of Life
Lymphocytes

Keywords

  • ABC-transporter
  • Disease modifying anti rheumatic drugs-DMARDs
  • Methotrexate
  • MultiDrug resistance
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

MDR-1 and MRP-1 activity in peripheral blood leukocytes of rheumatoid arthritis patients. / Micsik, Tamás; Lőrincz, A.; Gál, János; Schwab, Richard; Peták, I.

In: Diagnostic Pathology, Vol. 10, No. 1, 216, 30.12.2015.

Research output: Contribution to journalArticle

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abstract = "Background: Rheumatoid Arthritis is a chronic disease leading to decreased quality of life with a rather variable response rate to Disease Modifying Anti Rheumatic Drugs. Methotrexate (MTX) is the gold standard therapy in Rheumatoid Arthritis. The Multidrug resistance Related Protein and Multi Drug Resistance protein 1, also called P-glycoprotein-170 transporters can alter the intracellular concentration of different drugs. Methotrexate is an MRP1 substrate and thus the functional activity of MRP1 might have a clinical impact on the efficiency of the Methotrexate-therapy in Rheumatoid Arthritis. Methods: We have compared the functional Multidrug Activity Factors (MAF) of the MDR1 and MRP1 transporters of Peripheral Blood Leukocytes of 59 Rheumatoid Arthritis patients with various response rate to MTX-therapy (MTX-responder, MTX-resistant and MTX-intolerant RA-groups) and 47 non-RA controls in six different leukocyte subpopulations (neutrophil leukocytes, monocytes, lymphocytes, CD4+, CD8+ and CD19+ cells). There was a decreased MAF of RA patients compared to non- Rheumatoid Arthritis patients and healthy controls in the leukocyte subpopulations. There was a significant difference between the MAF values of the MTX-responder and MTX intolerant groups. But we have not found significant differences between the MAF values of the MTX-responder and MTX-resistant Rheumatoid Arthritis -groups. Results: Our results suggest that MDR1 and MRP1 functional activity does not seem to affect the response rate to MTX-therapy of Rheumatoid Arthritis-patients, but it might be useful in predicting MTX-side effects. We have demonstrated the decreased functional MDR-activity on almost 60 Rheumatoid Arthritis patients, which can be interpreted as a sign of the immune-suppressive effect of the MTX-treatment.",
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AU - Gál, János

AU - Schwab, Richard

AU - Peták, I.

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