title: MDR-1 and MRP-1 activity in peripheral blood leukocytes of rheumatoid arthritis patients.
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.
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. micsikt@mail.korb1.sote.hu.
authors.forename: Tamás
authors.initials: T
authors.lastname: Micsik
authors.affiliation: Rational Drug Design Laboratories CRC, Semmelweis University, Budapest, Hungary. lorincz2.andras@ttk.mta.hu.|Institute Of Materials And Environmental Chemistry,Research Centre for Natural Sciences, Biological Nanochemistry Research Group, Hungarian Academy of Sciences, 1117 Budapest, Magyar tudósok körútja 2. 1519, P.O. Box 286, Budapest, Hungary. lorincz2.andras@ttk.mta.hu.
authors.forename: András
authors.initials: A
authors.lastname: Lőrincz
authors.affiliation: Department of Rheumatology, Bács-Kiskun County Hospital, Kecskemét, Budapest, Hungary. galj@kmk.hu.
authors.forename: János
authors.initials: J
authors.lastname: Gál
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd, Budapest, Hungary. schwab@kps.hu.
authors.forename: Richard
authors.initials: R
authors.lastname: Schwab
authors.affiliation: KPS Medical Biotechnology and Healthcare Services Ltd, Budapest, Hungary. Istvan.petak@oncompassmedicine.com.|Department of Medical Chemistry and Pathobiochemistry, Pathobiochemistry Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary. Istvan.petak@oncompassmedicine.com.
authors.forename: István
authors.initials: I
authors.lastname: Peták
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000097:blood; D018501:Antirheumatic Agents / Q000378:metabolism / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008727:Methotrexate / Q000378:metabolism / Q000627:therapeutic use; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000097:blood*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018501:Antirheumatic Agents; D015415:Biomarkers; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human; C421109:multidrug resistance-associated protein 1