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Serum levels of P-glycoprotein and persistence of disease activity despite treatment in patients with systemic lupus erythematosus

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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.

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Acknowledgements

The authors wish thank to IMSS Foundation (Fundacion IMSS, A.C.) for the support for the research. Also, the authors thank M.B., M.A., for her style correction of the manuscript

Funding

This project was financed by a Grant from the “Fondo en Investigación en Salud” del Instituto Mexicano del Seguro Social. Grant: FIS/IMSS/PROT/G14/1296. Dr Gonzalez-Lopez holds Fundacion IMSS, A.C research scholarship (Beca de Excelencia en Investigación 2016 por la Fundación IMSS, A. C.)

Author information

Author notes

  1. Edsaul Emilio Perez-Guerrero, Jorge Ivan Gamez-Nava, David Bonilla-Lara, Ana Rosa Rincón-Sánchez, Jessica Daniela Murillo-Vazquez, Maria Luisa Vazquez-Villegas & Laura Gonzalez-Lopez

    Present address: 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 and Affiliations

  1. 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

    Jorge Ivan Gamez-Nava & Arnulfo Hernan Nava-Zavala

  2. 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

    Jose Francisco Muñoz-Valle

  3. Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Sierra Mojada 950, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico

    Ernesto German Cardona-Muñoz, Teresa Arcelia Garcia-Cobian, David Cardona-Müller & Sylvia Elena Totsuka-Sutto

  4. 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

    Nicte Selene Fajardo-Robledo

  5. Departamento de Inmunología y Reumatología, Hospital General de Occidente, Secretaria de Salud, Av Zoquipan 1050, Seattle, 45170, Zapopan, Jalisco, Mexico

    Arnulfo Hernan Nava-Zavala

  6. Programa Internacional de Medicina, Universidad de Autónoma de Guadalajara, Av. Patria 1201, Col. Lomas del Valle, 45129, Zapopan, Jalisco, Mexico

    Arnulfo Hernan Nava-Zavala

  7. 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

    Maria Luisa Vazquez-Villegas

  8. 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

    Laura Gonzalez-Lopez

  9. Avenida Salto del Agua 2192, Colonia Jardines del Country, 44210, Guadalajara, Mexico

    Laura Gonzalez-Lopez

Authors
  1. Edsaul Emilio Perez-Guerrero
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  2. Jorge Ivan Gamez-Nava
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  3. Jose Francisco Muñoz-Valle
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  4. Ernesto German Cardona-Muñoz
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  5. David Bonilla-Lara
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  6. Nicte Selene Fajardo-Robledo
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  7. Arnulfo Hernan Nava-Zavala
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  8. Teresa Arcelia Garcia-Cobian
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  9. Ana Rosa Rincón-Sánchez
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  10. Jessica Daniela Murillo-Vazquez
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  11. David Cardona-Müller
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  13. Sylvia Elena Totsuka-Sutto
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  14. Laura Gonzalez-Lopez
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Corresponding author

Correspondence to Laura Gonzalez-Lopez.

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Authors declare that they have no conflict of interest.

Ethical approval

This study was conducted according to the recommendations described by the 64th Declaration of Helsinki and was in accordance with the ethical standards of the Ethics and Research Board of UMAE Centro Medico Nacional de Occidente del Instituto Mexicano del Seguro Social (13-01 with approval code: R-2014-1301-77).

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Informed consent was obtained from all individual participants included in the study.

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Perez-Guerrero, E.E., Gamez-Nava, J.I., Muñoz-Valle, J.F. et al. Serum levels of P-glycoprotein and persistence of disease activity despite treatment in patients with systemic lupus erythematosus. Clin Exp Med 18, 109–117 (2018). https://doi.org/10.1007/s10238-017-0459-0

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  • DOI: https://doi.org/10.1007/s10238-017-0459-0

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