The Molecular Mechanism Of Multidrug Resistance In Refractory Rheumatoid Arthritis

Objective:To detect the P-glycoprotein (P-gp),breast-cancer resistance protein(BCRP) and Pim-1 expression of peripheral blood lymphocytes in rheumatoid arthritis (RA) in early untreated group, treatment group and the refractory patients and explore the possible mechanisms of multidrug resistance in refractory RA.Method:Patients were divided into RA in early untreated group, treatment group and 20 cases of refractory group based on the standard of enrollement. Flow cytometry with indirect immunofluorescence assay was used to measure the peripheral blood lymphocytes P-gp.The expressions of BCRP and Pim-1 in refractory RA in early untreated group, treatment group and the normal were observed by immunocytochemical technique. LSD-t test,Chi-square test,oneway-ANOVA and likelihood ratio test for statistical anglysis.Results:1. The peripheral blood lymphocytes P-gp expression fluorescence value (4.26±0.47) of the RA early untreated group was significantly increased when compared to the normal control group (4.03±0.34)(t=1.26,P>0.05).2. The peripheral blood lymphocyte P-gp expression fluorescence value of the RA treatment group(6.74±0.23) was mildly increased when compared with the normal control group and untreated early RA group, but the difference was significant(t=21.20, P<0.05).3. The peripheral blood lymphocytes P-gp expression fluorescence value of the RA refractory (13.10±0.33) were markedly increased when compared with that of the normal control group, the untreated early RA group and RA treatment group and the difference was significant(t=85.60, P＜0.05).4. The percentage of BCRP expression in peripheral blood lymphocytes of refractory RA, early untreated RA, effective treatment RA and normal group, the positive expression of BCRP was 2(10%), 1(5%),0(0%) and 0(0%). No significant difference was identified (P>0.05).5. The percentage of Pim-1 kinase expression in peripheral blood lymphocytes of refractory RA, early untreated RA, effective treatment RA and normal group, the positive expression of Pim-1 kinase was 1(5%), 0(0%),1(5%) and 0(0%). No significant difference was identified (P>0.05).Conclusion:1. The expression level of P-gp of the peripheral blood lymphocytes of the early RA untreated is not significantly increased compared with control group. For those patients who did not receive prompt treatment did not develop resistance.2. Methotrexate, leflunomide in the treatment of rheumatoid arthritis can induce the expression of P-glycoprotein in the peripheral blood lymphocytes which in turn leading to drug-resistance.3. P-gp is involved in of the multidrug resistance of refractory RA and may be one of the possible mechanisms.4. BCRP and Pim-1 kinase are no significant correlation with RA refractory to form multidrug resistance mechanisms.