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• W1991784973 abstract "Abstract Objective To determine whether multidrug‐resistance efflux transporters are expressed on immune effector cells in synovial tissue from patients with rheumatoid arthritis (RA) and compromise the efficacy of methotrexate (MTX) and leflunomide (LEF). Methods Synovial tissue biopsy samples obtained from RA patients before treatment and 4 months after starting treatment with MTX (n = 17) or LEF (n = 13) were examined by immunohistochemical staining and digital image analysis for the expression of the drug efflux transporters P‐glycoprotein, multidrug resistance–associated protein 1 (MRP‐1) through MRP‐5, MRP‐8, MRP‐9, and breast cancer resistance protein (BCRP), and the relationship to clinical efficacy of MTX and LEF was assessed. Results BCRP expression was observed in all RA synovial biopsy samples, both pretreatment and posttreatment, but not in control noninflammatory synovial tissue samples from orthopedic patients. BCRP expression was found both in the intimal lining layer and on macrophages and endothelial cells in the synovial sublining. Total numbers of macrophages in RA patients decreased upon treatment; in biopsy samples with persistently high macrophage counts, 2‐fold higher BCRP expression was observed. Furthermore, median BCRP expression was significantly increased (3‐fold) in nonresponders to disease‐modifying antirheumatic drugs (DMARDs) compared with responders to DMARDs ( P = 0.048). Low expression of MRP‐1 was found on synovial macrophages, along with moderate expression in T cell areas of synovial biopsy specimens from one‐third of the RA patients. Conclusion These findings show that the drug resistance–related proteins BCRP and MRP‐1 are expressed on inflammatory cells in RA synovial tissue. Since MTX is a substrate for both BCRP and MRP‐1, and LEF is a high‐affinity substrate for BCRP, these transporters may contribute to reduced therapeutic efficacy of these DMARDs." @default.
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• W1991784973 date "2009-02-26" @default.
• W1991784973 modified "2023-10-18" @default.
• W1991784973 title "Involvement of breast cancer resistance protein expression on rheumatoid arthritis synovial tissue macrophages in resistance to methotrexate and leflunomide" @default.
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• W1991784973 doi "https://doi.org/10.1002/art.24354" @default.
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