Study Of Expression Of Peripheral Blood Lymphocyte P-glycoprotein And Its Reversion In Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is a common systematic autoimmune disease which characteristic is chronic symmetrical polyarthritis. Now, the most important treatment of RA is disease modifying anti-rheumatic drugs (DMARDs). But the efficacies of DMARDs could decrease gradually because of cell's drug resistance. The study of drug resistance has been started in tumor and anti-infection research area, which is a new area in RA treatment. Among of all studies about the mechanism of drug resistance, the study of P-glycoprotein (P-gp) mediated multidrug resistance is more. Through over 10 year's clinical and empirical research, the synergistic effect of the therapeutic alliance of MTX and CTX is confirmed. So in terms of P-gp mediated multidrug resistance, we study the mechanism of synergistic effect of MTX and CTX to confirm their therapeutic alliance can overcome drug resistance.Objective1. To study the difference between the expression of peripheral blood lymphocyte P-gp in naive RA groups and the one in healthy controls.2. To study the difference between the expression of peripheral blood lymphocyte P-gp in RA improvement group and the one in RA refractoriness group.3. To investigate the disease association factor of the expression of peripheral blood lymphocyte P-gp in RA.4. To investigate the expression reversion of peripheral blood lymphocyte P-gp by the therapeutic alliance of DMARDs in RA.MethodsThe study was a cross-sectional one. 42 RA patients were collected according to the RA diagnostic criteria of American College of Rheumatology (ACR) in 1987. They divided into two groups, 15 cases in naive group and 27 cases in treatment group. According to their disease activity scores (DAS28) in 4 months, treatment group divided into improvement group (12 patients) and refractoriness group (15 patients). Besides, 15 health persons were chosen to be a control group. The expression of peripheral blood lymphocyte P-gp in each group was detected by flow cytometry and measured by mean relative fluorescence intensity (RFI). According to their therapeutic regimen, treatment group (including 27 cases) were separated into 3 groups, 8 cases in MTX/LEF group, 5 cases in MTX+LEF group and 14 cases in MTX/LEF + CTX group. RFI in three groups was compared and analyzed.Results1. RFI of peripheral blood lymphocyte P-gp in control group was 2.0, the one in naive groupwas 2.9, the latter was 45% higher than the former (P<0.05).2. RFI of peripheral blood lymphocyte P-gp in naive group and treatment group was respectively 2.9 and 4.1. The difference between the two had statistical significance (P<0.05).3. RFI of peripheral blood lymphocyte P-gp in improvement group and refractoriness group was respectively 3.5 and 5.0, the latter was 42.9% higher than the former (P=0.06).4. There was no correlation between the expression of peripheral blood lymphocyte P-gp in RA patients and sex, age of onset, disease duration or positive rate of RF. But the expression of peripheral blood lymphocyte P-gp was significantly correlated with ESR and DAS28 (P<0.05).5. RFI of peripheral blood lymphocyte P-gp in MTX/LEF group, MTX+LEF group and MTX/LEF + CTX group was respectively 5.1, 6.0 and 3.4 (P<0.05). Through pairwise comparison, P-gp expression of MTX/LEF+CTX group is lower than that of MTX/LEF group (P<0.05) .Conclusions1. The expression of peripheral blood lymphocyte P-gp is parallel with disease activity of RA, which associates with the therapeutic effects of DMARDs;2. The expression of peripheral blood lymphocyte P-gp in MTX/LEF + CTX group is lower than that in MTX/LEF monotherapy. To a certain extent, the therapeutic alliance of MTX/LEF + CTX reverses the expression of P-gp in RA.