Phénotype MDR-I de multirésistance aux traitements de fond dans les maladies rhumatismales auto-immunes: Deuxième partie : une activité accrue de la P-glycoprotéine lymphocytaire semble s'accompagner de besoins plus importants en glucocorticoïdes dans le lupus érythémateux disséminé

Abstract

Background. Over-expression of the membrane glycoprotein called P-glycoprotein has been widely observed in a variety of both normal and neoplastic cells. P-glycoprotein is a pump molecule that transports hydrophobic drugs (including steroids) and toxins outside the cell, thus inhibiting their therapeutic or toxic effects. The gene encoding P-glycoprotein is named multidrug resistance-I (MDR-I). Objective. To evaluate the functional activity of P-glycoprotein in lymphocytes and monocytes from patients with systemic lupus erythematosus. Subjects and methods. 30 systemic lupus erythematosus patients and 20 healthy controls were studied. Peripheral blood mononuclear cells isolated by gradient centrifugation were incubated in the presence of daunorubicin (a fluorescent drug extruded by P-glycoprotein) at 37° C or 4° C for 30 min. P-glycoprotein activity was then analyzed using flow cytometry. Results were expressed as the percentage of lymphocytes or monocytes with high P-glycoprotein activity (i.e., low fluorescence). Results. Mean fluorescence values for lymphocytes and monocytes were comparable between patients and healthy controls. However, because our method allowed to measure P-glycoprotein function at the single-cell level, we were able to show that the mean percentage of lymphocytes with high P-glycoprotein activity was increased in the patients (11.51 % ± 14.3%) as compared to the healthy controls (0.71% ± 0.57%) (P < 0.05). Moreover, P-glycoprotein activity was lower in the patients in clinical remission than in those with active disease. Conclusions. Our results suggest that P-glycoprotein function might affect glucocorticoid requirements in systemic lupus erythematosus.