title: P-glycoprotein-1 functional activity in CD5+CD7+ and CD20+ lymphocytes in systemic lupus erythematosus children: relation to disease activity, complications and steroid response.
abstract: The multi-drug resistance protein -1 or P-glycoprotein-1 ( P-gp1) functions as Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. Increased P-gp1 expression in lymphocytes of patients with systemic lupus erythematosus (SLE) may influence steroid requirements for disease control. This study evaluates P-gp1 functional activity in CD5+, CD7+ and CD20+ lymphocytes in SLE children and its impact on clinical outcome. 44 SLE children and 50 healthy controls were studied. Estimation of P-gp1 function was based on the efflux of Rhodamine-123 using flow cytometry. Results were expressed as percentage of lymphocytes with high P-gp1 activity. The P-gp1 function in CD5+, CD7+ and CD20+ lymphocytes was significantly higher in patients compared to controls (with P value < 0.05 for each lymphocyte population). The expression of active P-gp1 in CD5+ and CD7+ lymphocytes correlated positively with disease activity as estimated by SLEDAI and ESR. P-gp1 expression in SLE lymphocytes was also found to correlate significantly with some disease manifestations specially lupus nephritis, thrombocytopenia and ANA positivity. Steroids low responders whose SLEDAI were > or = 11 while receiving 1 mg/Kg/day of prednisolone demonstrated higher P-gp1 functions in CD 5+ and CD 7+ lymphocytes compared to high responders whose SLEDAI were < 11 while receiving < 1 mg/Kg/day of prednisolone. CD5+ lymphocyte's P-gp1 function was found to be lower in the patients receiving cyclophosphamide in addition to steroids compared to those on steroids only. It is concluded that measuring P-gp1 function in CD5+ and CD7+ lymphocytes could be one of the prognostic and therapeutic indices in SLE.
authors.forename: Seham M
authors.initials: SM
authors.lastname: Ragab
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Soliman
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology*; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000032:analysis*; D019011:Antigens, CD7 / Q000032:analysis*; D001799:Blood Sedimentation; D018956:CD5 Antigens / Q000032:analysis*; D002648:Child; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D012720:Severity of Illness Index; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000305:Adrenal Cortex Hormones; D018951:Antigens, CD20; D019011:Antigens, CD7; D018956:CD5 Antigens; D000097202:ATP-Binding Cassette Sub-Family B Member 4