Background Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease, where the treatment includes corticosteroids, DMARD-s and newly developed biological agents, but we often face drug resistance and thus inefficiency. One particular mechanism of loss of drug efficacy is multi-drug resistance (MDR), i.e. over-activity of drug efflux pumps, that belongs to the ATP binding cassette super family, such as ABCB1 (P-gp, MDR1), ABCC1 (MRP1) and ABCG2 (BCRP, MXR). Results from the literature reveal that expressions of different transporters are correlating with disease activity in different lymphocytes populations, but data from functional activities have conflicting results.
Objectives Determination of functional activity of the MDR transporters in newly recognized not treated “naïve” active, active and inactive patients with SLE, comparison the results with the data of healthy individuals. Study the effect of corticosteroid and DMARD therapies on the activity of the MDR transporters.
Methods PBMC-s of patients with SLE and control populations were isolated, then CD3 positive cells were further investigated via a flow cytometric analysis. The activity of the multidrug transporter (MAF) was calculated from the difference between the mean fluorescent intensity of cells without the specific inhibitors, respectively. MAF was determined in the study populations before and after corticosteroid and/or DMARD treatments (active groups), or once (inactive and control groups). The SOLVO MDQ Kit™ was used to detect the functional activity of clinically relevant MDR1, MRP1 and BCRP efflux transporters in the cells.
Results The CD3+ cells of total number of 87 patients with SLE were investigated. 12 patients were therapy free “naïve” active (SLEDAI: 12.5), 12 patients were previously treated, but currently active patients (SLEDAI: 7.58) and 63 patients were in inactive phase of the disease (SLEDAI: 2.64). Lymphocytes of 120 age and sex matched healthy individuals were tested as a control population. We could detect, that the MAF results of the SLE patients were comparable to the control population. We could not find significant differences in the three different patient populations, regarding the transporter activity. No significant correlations were found between the disease activity, i.e. SLEDAI score, and the transporter activities. Analyzing the therapy naïve active population revealed that corticosteroid treatment significantly decreased disease activity but no changes were detected in the functional activity of the transporters. Similarly, new DMARD therapy introduction in the active patients did not alter the MAF results of the transporters.
Conclusions Our data suggest that neither disease activity, nor immunosuppressant treatment modify functional activity of MDR transporters in the CD3 positive T-cells of patients with SLE.
Disclosure of Interest None Declared
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