Multidrug resistance-1 (MDR-1) in autoimmune disorders III: increased P-glycoprotein activity in lymphocytes 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.


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.


CONCLUSIONS
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.
Ruiz-Soto
Rodrigo
R
Department of Hematology,Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan, C.P. 14000 Mexico City, DF, Mexico.
Richaud-Patin
Yvonne
Y
López-Karpovitch
Xavier
X
Llorente
Luis
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D016022:Case-Control Studies; D003630:Daunorubicin / Q000493:pharmacokinetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000378:metabolism / Q000473:pathology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers; D003630:Daunorubicin