title: Serum levels of P-glycoprotein and persistence of disease activity despite treatment in patients with systemic lupus erythematosus.
abstract: Around 25% of patients with systemic lupus erythematosus (SLE) could be refractory to conventional therapies. P-glycoprotein expression on cell surface has been implied on drug resistance, however, to date, it is unknown if P-gp serum levels are associated with SLE disease activity. Evaluate the association of serum P-gp levels and SLE with disease activity despite treatment. A cross-sectional study was conducted on 93 female SLE patients, all receiving glucocorticoids at stable doses for the previous 6 months before to baseline. SLE patients were classified into two groups: (a) patients with active disease [SLE disease activity index (SLEDAI) ≥ 3] despite treatment, and (b) patients with inactive disease (SLEDAI < 3) after treatment. Forty-three healthy females comprised the control group. Serum P-gp, anti-DNA, and both anti-nucleosome antibody levels were measured using ELISA. Active-SLE patients despite treatment had higher P-gp levels compared with inactive-SLE after treatment (78.02 ng/mL ± 114.11 vs. 33.75 ng/mL ± 41.11; p = 0.018) or versus reference group subjects (30.56 ng/mL ± 28.92; p = 0.011). P-gp levels correlated with the scores of SLEDAI (r = 0.26; p = 0.01), Mexican-SLEDAI (MEX-SLEDAI) (r = 0.32; p = 0.002), SLICC/ACR damage index (r = 0.47; p < 0.001), and with prednisone doses (r = 0.33; p = 0.001). In the multivariate model, the high P-gp levels were associated with SLICC/ACR score (p = 0.001), and SLEDAI score (p = 0.014). Our findings support a relationship between serum P-gp levels and SLE with disease activity despite treatment, but it requires further validation in longitudinal studies.
authors.affiliation: Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Edsaul Emilio
authors.initials: EE
authors.lastname: Perez-Guerrero
authors.affiliation: Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.|Unidad de Investigación Biomédica 02 (UIEC), UMAE Hospital de Especialidades, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Avenida Belisario Domínguez 1000, Col. Independencia Oriente, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Jorge Ivan
authors.initials: JI
authors.lastname: Gamez-Nava
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Jose Francisco
authors.initials: JF
authors.lastname: Muñoz-Valle
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Ernesto German
authors.initials: EG
authors.lastname: Cardona-Muñoz
authors.affiliation: Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Bonilla-Lara
authors.affiliation: Laboratorio de Investigación y Desarrollo Farmacéutico, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Blvd. Marcelino García Barragán 421, 44430, Guadalajara, Jalisco, Mexico.
authors.forename: Nicte Selene
authors.initials: NS
authors.lastname: Fajardo-Robledo
authors.affiliation: Unidad de Investigación Biomédica 02 (UIEC), UMAE Hospital de Especialidades, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Avenida Belisario Domínguez 1000, Col. Independencia Oriente, 44340, Guadalajara, Jalisco, Mexico.|Departamento de Inmunología y Reumatología, Hospital General de Occidente, Secretaria de Salud, Av Zoquipan 1050, Seattle, 45170, Zapopan, Jalisco, Mexico.|Programa Internacional de Medicina, Universidad de Autónoma de Guadalajara, Av. Patria 1201, Col. Lomas del Valle, 45129, Zapopan, Jalisco, Mexico.
authors.forename: Arnulfo Hernan
authors.initials: AH
authors.lastname: Nava-Zavala
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Teresa Arcelia
authors.initials: TA
authors.lastname: Garcia-Cobian
authors.affiliation: Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Rincón-Sánchez
authors.affiliation: Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Jessica Daniela
authors.initials: JD
authors.lastname: Murillo-Vazquez
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Cardona-Müller
authors.affiliation: Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.|Unidad Médica Familiar 4 y 8, Departamento de Epidemiologia, Instituto Mexicano del Seguro Social (IMSS), Fidel Velázquez Sánchez 1531, Atemajac del Valle, 44218, Guadalajara, Jalisco, Mexico.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Vazquez-Villegas
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: Sylvia Elena
authors.initials: SE
authors.lastname: Totsuka-Sutto
authors.affiliation: Programa de Doctorado en Farmacologia, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico. dralauragonzalez@prodigy.net.mx.|Departamento de Medicina Interna-Reumatología, Instituto Mexicano del Seguro Social (IMSS), Hospital General Regional 110, Av Circunvalación Oblatos 2208, Colonia Circunvalación Oblatos, 44716, Guadalajara, Jalisco, Mexico. dralauragonzalez@prodigy.net.mx.|, Avenida Salto del Agua 2192, Colonia Jardines del Country, 44210, Guadalajara, Mexico. dralauragonzalez@prodigy.net.mx.
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0002-6517-6344
authors.initials: L
authors.lastname: Gonzalez-Lopez
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000097:blood; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000473:pathology*; D008875:Middle Aged; D044967:Serum / Q000737:chemistry*; D012720:Severity of Illness Index; D014838:Volunteers; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000974:Antibodies, Antinuclear; D005938:Glucocorticoids; D007166:Immunosuppressive Agents
keywords: Disease activity; Drug resistance; Glucocorticoids; P-glycoprotein; Systemic lupus erythematosus