title: Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus.
abstract: Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of medical Sciences, Raebareli Road, Lucknow, 226014, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kansal
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of medical Sciences, Raebareli Road, Lucknow, 226014, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Tripathi
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of medical Sciences, Raebareli Road, Lucknow, 226014, India.
authors.forename: Mohit K
authors.initials: MK
authors.lastname: Rai
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of medical Sciences, Raebareli Road, Lucknow, 226014, India. vikasagr@yahoo.com.
authors.forename: Vikas
authors.initials: V
authors.lastname: Agarwal
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D006886:Hydroxychloroquine; D011239:Prednisolone
keywords: Corticosteroids; Multidrug resistance; P-glycoprotein; Systemic lupus erythematosus