Multidrug resistance-1 (MDR-1) in autoimmune disorders III: Increased P-glycoprotein activity inlymphocytes from immune thrombocytopenic purpura patients

Objective. P-glycoprotein (P-gp) expression has been widely observed in normal and neoplastic cells. The physiologic role of P-gp involves hormone and metabolite secretion, bacterial product detoxification, and transport of several drugs to the extracellular space. Multidrug resistance-1 is characterized by drug extrusion through P-gp, reducing the intracellular levels of drugs and diminishing their pharmacological effects. Treatment of immune thrombocytopenic purpura (ITP) includes agents that are substrates of P-gp; hence, the objective of this study was to analyze the functional activity of P-gp in lymphocytes from patients with ITP. Patients and Methods. 30 ITP patients (9 refractory, 5 dependent, 14 responders to treatment, and 2 with stable disease) and 25 healthy controls were studied. Peripheral blood mononuclear cells were isolated by gradient centrifugation and incubated with daunorubicin (a fluorescent drug extruded by P-gp). Functional activity of P-gp was analyzed by flow cytometry. Results were expressed as the percentage of lymphocytes able to extrude daunorubicin. Results. ITP patients showed an increased number of lymphocytes with P-gp activity (mean = 12.3%±16%) when compared to controls (mean = 0.87%±0.72%) (p<0.05). P-gp function was higher in the refractory group (median = 9.4%) than in the treatment-dependent (median = 5.4%), responder (median = 6.4%), and stable disease (median = 5.2%) groups, although no statistical differences were found among them. Conclusion. Enhanced P-gp activity in ITP may be related to an unfavorable clinical outcome and poor response to treatment. Furthermore, P-gp function might affect therapeutic requirements for disease control.