title: Rheumatoid Arthritis Disease Activity Is Determinant for ABCB1 and ABCG2 Drug-Efflux Transporters Function.
abstract: OBJECTIVE
  To compare drug efflux function of ABCB1 and ABCG2 transporters in rheumatoid arthritis (RA) patients with active disease and in remission.
  
  
  METHODS
  Twenty two active RA patients (DAS28 ≥3.2) and 22 patients in remission (DAS28<2.6) were selected from an early RA clinic. All patients were evaluated at study inclusion and six months later. ABCB1 and ABCG2 functional activity was measured in peripheral lymphocytes by flow cytometry. The percentage of cells able to extrude substrates for ABCB1 and ABCG2 was recorded.
  
  
  RESULTS
  Active patients had higher ABCB1 and ABCG2 activity compared with patients in remission (median [interquartile range]): 3.9% (1.4-22.2) vs (1.3% (0.6-3.2), p = 0.003 and 3.9% (1.1-13.3) vs 0.9% (0.5-1.9) p = 0.006 respectively. Both transporters correlated with disease activity assessed by DAS28, rho = 0.45, p = 0.002 and rho = 0.47, p = 0.001 respectively. Correlation was observed between the time from the beginning of treatment and transporter activity: rho = 0.34, p = 0.025 for ABCB1 and rho = 0.35, p = 0.018 for ABCG2. The linear regression model showed that DAS28 and the time from the onset of treatment are predictors of ABCB1 and ABCG2 functional activity, even after adjustment for treatment. After six months we calculated the correlation between change in DAS28 and change in the functional activity in both transporters and found a moderate and significant correlation for ABCG2 (rho = 0.28, p = 0.04) and a non-significant correlation for ABCB1 (rho = 0.22, p = 0.11).
  
  
  CONCLUSIONS
  Patients with active RA have an increased function of ABCB1 and ABCG2, and disease activity is the main determinant of this phenomena.
authors.affiliation: Division of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Yemil
authors.initials: Y
authors.lastname: Atisha-Fregoso
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Lima
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual-Ramos
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Miguel
authors.initials: M
authors.lastname: Baños-Peláez
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Hilda
authors.initials: H
authors.lastname: Fragoso-Loyo
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Juan
authors.initials: J
authors.lastname: Jakez-Ocampo
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Irazú
authors.initials: I
authors.lastname: Contreras-Yáñez
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
authors.forename: Luis
authors.initials: L
authors.lastname: Llorente
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000378:metabolism*; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000378:metabolism*; D001692:Biological Transport; D003630:Daunorubicin / Q000378:metabolism; D003710:Demography; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D016014:Linear Models; D008297:Male; D008942:Mitoxantrone / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D012074:Remission Induction; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D009363:Neoplasm Proteins; D008942:Mitoxantrone; D003630:Daunorubicin