Abstract
The objective of this study was to assess the expression of a multidrug resistance (MDR) phenotype, implicated in the cellular resistance of tumor to chemotherapy, in rheumatoid synovial membrane. Synovial membrane from 16 rheumatoid (RA) patients was studied. Six patients with osteoarthritis constituted the control group. The cell membrane expression of the glycoprotein Pgp 170, encoded by the MDR 1 gene, was determined by an immunoperoxidase technique using two different monoclonal antibodies (JSB 1, C219). The polymeras chain reaction (PCR) methods were used in parallel to detect the presence of the MDR 1 gene mRNA in the synovial cells. Pgp 170 was expressed on the cell membrane of five RA patients and MDR 1 cellular transcription was detected in one other RA patient. We did not observe any association between synovial glycoprotein expression and age, disease activity, and a specific treatment with a long-acting drug. However, MDR protein expression was associated with the successive treatment with more than three disease-modifying antirheumatic drugs (DMARDs). We conclused that the synovial membrane expresses a glycoprotein recognized by the antibodies JSB 1 and C219. The absence of concomitant MDR 1 transcription suggests the expression of an atypical MDR phenotype in the synovial membrane, distinct from the Pgp 170 encoded by the MDR 1 gene. The implications of the MDR phenotype and the resistance of RA to DMARDs is further discussed.
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References
Flier JS, Underhill LH (1987) Multiple drug resistance in human cancer. N Engl J Med 316:1388–1393
Kartner N, Riordan JR, Ling V (1983) Cell surface P glycoprotein associated with multiple-drug resistance in mammalian cell lines. Science 221:1285–1288
Gottesman MM, Pastan I (1988) The multidrug transporter, a double edged sword. J Biol Chem 263:12163–12166
Gordon-Cardo C, O'Brien JP, Boccia J, Casals D, Bertino JR, Melamed MR (1990) Expression of the multiple drug resistance gene product (P glycoprotein) in human normal and tumor tissues. Histo Chem Cytochem 38:1277–1283
Drach D, Zhao S, Drach J, Mahadevia R, Gattringer C, Huber H, Andreeff M (1992) Subpopulations of normal peripheral blood and bone marrow cells express a functional multidrug resistant phenotype. Blood 11:2729–2735
Glennas A, Rugstad HR (1985) Acquired resistance to auranofin in cultured human cells. Scand J Rheumatol 14:230–238
Rodenhuis S, Kremer JM, Bertino JR (1987) Increase of dihydrofolate reductase in peripheral blood lymphocytes of RA treated with low dose oral methotrexate. Arthritis Rheum 30: c369–374
Norris MD, Haber M, King M, Davey R (1989) Atypical multidrug resistance in CCRF-CEM cells selected for high level methotrexate resistance: reactivity to monoclonal antibody C219 in the absence of P-glycoprotein expression. Biochem Biophys Res Commun 165:1435–1441
Arnett FC, Edworthy SM, Bloch DA (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Ritchie PM, Boyle JA, McInnes JM (1969) Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 11:393–406
Chomoczynski P, Sacchin N (1987) Single step method of RNA isolation by acid guandinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Zhang YH, McCabe ER (1992) RNA analysis from newborn screening dried blood specimens. Hum Genet 89:311–34
Fuqua SA, Fitzgerald SD, McGuire WL (1990) A simple polymerase chain reaction method for detection and cloning of low abundance transcription. Biotechniques 9:206–211
Goldstein LJ, Galski H, Fojo A, Willingham M, Kai SL, Pastan I (1989) Expression of a multiple resistance gene in human cancers. J Natl Cancer Inst 81:116–124
Noonan KE, Beck C, Holzmayer TA, Chin JE, Wunder JS, Andrulis JL, Roninson IB (1990) Quantitative analysis of MDR 1 gene expression in human tumors by polymerase chain reaction. Proc Natl Acad Sci 87:7160–7164
Grogan TM, Spier CM, Salmon SE (1993) P-glycoprotein expression in human plasma cell myeloma: correlation with prior chemotherapy. Blood 81:490–495
West IC (1990) What determines the substrate specificity of the multi-drug-resistance pump? Trends Biochem Sci 15:42–46
Linsenmeyer ME, Jefferson S, Wolf M, Matthews JP, Board PG, Woodcock DM (1992) Levels of expression of the MDR 1 gene and glutathion S transferase genes 2 and 3 and response to chemotherapy in multiple myeloma. Br J Cancer 65:471–475
Assaraf YG, Slotky JI (1993) Characterization of a lipophilic antifolate resistance provoked by treatment of mammalian cells with the antiparasitic agent pyrimethamine. J Biol Chem 268:4556–4566
Sonnefeld P, Durie BG, Lockhorst HK, Marie JP (1992) Modulation of multidrug resistance multiple myeoloma by cyclosporin. Lancet 340:255–259
Tugwell P, Pincus T, Yocum D, Wells G, McKendry R, Kraag G, Baker P (1994) A multi-center double blind randomized trial of low dose cyclosporin and placebo therapy in combination with methotrexate in patients with severe rheumatoid arthritis (abstract). Arthritis Rheum 37:S 391
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Jorgensen, C., Sun, R., Rossi, J.F. et al. Expression of a multidrug resistance gene in human rheumatoid synovium. Rheumatol Int 15, 83–86 (1995). https://doi.org/10.1007/BF00262714
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DOI: https://doi.org/10.1007/BF00262714