Study of the expression of peripheral blood lymphocyte P-glycoprotein in rheumatoid arthritis patients and reversing P-glycoprotein-induced drug resistance / 中华风湿病学杂志

ABSTRACT

Objective To study the expression of peripheral blood lymphocyte P-glycoprotein(P-gp)and related impact factors in rheumatoid arthritis(RA)patients,and explore whether the periodic combination of methotrexate(MTX)or leflunomide(LEF)with cyclophosphamide(CTX)could reverse P-gpinduced drug resistance.Methods This study was a cross-sectional study.Forty-two RA patients were enrolled(15 cases in the primary untreatment group,while 27 cases in the treatment group).In the treatment group,patients were divided into the improvement group(12 patients)and the refractory group(15 patients)respectively according to their disease activity scores(DAS 28).According to the medication used,42 patients were divided into 3 groupsthe monotherapy group(MTX or LEF),the MTX+LEF combination treatment group and MTX or LEF+CTX treatment group.The expression of peripheral blood lymphocyte P-gp in each group was detected by flow cytometry.T test,ANOVA,LSD test,Bonferroni test,x2 test and Pearson correlation analysis were used for statistical analysis with software 13.0.Results ① Mean relative fluore scence intensity(RFI)of P-gp was 2.0±0.7,2.9±1.0,3.5±1.4,5.0±2.0 respectively in healthy control group,the primary untreatment group,the improvement group and the refractory group,the difference was significant(F=7.955,P＜0.01).in multiple comparisons,the fluorescence intensity was higher in the primary untrea-tment group as compared to the healthy group,but the difference was not statistically significant(P=0.137);however,it was significantly higher in the refractory group as compared to the improvement group(P=0.013).② There was no correlation between the expression of P-gp in RA patients and sex,age of onset,disease duration or positive rate of RF.But the expression of P-gp was significantly correlated with ESR and DAS28(r=0.447,P=0.002;r=0.398,P=0.012).③ RFI of the P-gp group was 5.1±2.2,6.0±1.2,3.4±1.1 respectively in monotherapy group,MTX+LEF group and MTX/LEF+ CTX group(P＜0.05).The expression of P-gp was significantly lower in the MTX/LEF+CTX group as compared to the monotherapy group(P＜0.05),but higher in the MTX+LEF group(P＞0.05).Conclusion The expression of peripheral blood lymphocyte P-gp in RA is correlated with disease activity.The loss of efficacy in DMARDs is due to the enhanced expression of P-gp.Combination of methotrexate or leflunomide with cyclo-phosphamide reverses P-glycoproteininduced drug resistance.