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Clinical and Experimental Medicine

, Volume 18, Issue 1, pp 109–117 | Cite as

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

  • Edsaul Emilio Perez-Guerrero
  • Jorge Ivan Gamez-Nava
  • Jose Francisco Muñoz-Valle
  • Ernesto German Cardona-Muñoz
  • David Bonilla-Lara
  • Nicte Selene Fajardo-Robledo
  • Arnulfo Hernan Nava-Zavala
  • Teresa Arcelia Garcia-Cobian
  • Ana Rosa Rincón-Sánchez
  • Jessica Daniela Murillo-Vazquez
  • David Cardona-Müller
  • Maria Luisa Vazquez-Villegas
  • Sylvia Elena Totsuka-Sutto
  • Laura Gonzalez-LopezEmail author
Original Article

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.

Keywords

Drug resistance P-glycoprotein Glucocorticoids Systemic lupus erythematosus Disease activity 

Notes

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.)

Compliance with ethical standards

Conflict interest

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).

Informed consent

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

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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Edsaul Emilio Perez-Guerrero
    • 1
  • Jorge Ivan Gamez-Nava
    • 1
    • 2
  • Jose Francisco Muñoz-Valle
    • 3
  • Ernesto German Cardona-Muñoz
    • 4
  • David Bonilla-Lara
    • 1
  • Nicte Selene Fajardo-Robledo
    • 5
  • Arnulfo Hernan Nava-Zavala
    • 2
    • 6
    • 7
  • Teresa Arcelia Garcia-Cobian
    • 4
  • Ana Rosa Rincón-Sánchez
    • 1
  • Jessica Daniela Murillo-Vazquez
    • 1
  • David Cardona-Müller
    • 4
  • Maria Luisa Vazquez-Villegas
    • 1
    • 8
  • Sylvia Elena Totsuka-Sutto
    • 4
  • Laura Gonzalez-Lopez
    • 1
    • 9
    • 10
    Email author
  1. 1.Programa de Doctorado en FarmacologiaCentro Universitario de Ciencias de la Salud (CUCS), Universidad de GuadalajaraGuadalajaraMexico
  2. 2.Unidad de Investigación Biomédica 02 (UIEC), UMAE Hospital de Especialidades, Centro Médico Nacional de OccidenteInstituto Mexicano del Seguro SocialGuadalajaraMexico
  3. 3.Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS)Universidad de GuadalajaraGuadalajaraMexico
  4. 4.Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS)Universidad de GuadalajaraGuadalajaraMexico
  5. 5.Laboratorio de Investigación y Desarrollo Farmacéutico, Centro Universitario de Ciencias Exactas e IngenieríasUniversidad de GuadalajaraGuadalajaraMexico
  6. 6.Departamento de Inmunología y ReumatologíaHospital General de Occidente, Secretaria de SaludZapopanMexico
  7. 7.Programa Internacional de MedicinaUniversidad de Autónoma de GuadalajaraZapopanMexico
  8. 8.Unidad Médica Familiar 4 y 8, Departamento de EpidemiologiaInstituto Mexicano del Seguro Social (IMSS)GuadalajaraMexico
  9. 9.Departamento de Medicina Interna-ReumatologíaInstituto Mexicano del Seguro Social (IMSS)GuadalajaraMexico
  10. 10.GuadalajaraMexico

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