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Clinical relevance of P-glycoprotein activity on peripheral blood mononuclear cells and polymorphonuclear neutrophils to methotrexate in systemic lupus erythematosus patients

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Abstract

To elucidate the relationship between P-glycoprotein activity on peripheral blood leukocytes of systemic lupus erythematosus (SLE) patients with lupus arthritis and the clinical response to methotrexate. An observational study was made in patients with SLE according to ACR criteria 1997 who had arthralgia and arthritis and received methotrexate for ≥3 months. Methotrexate responders and non-responders were compared according to the Clinical Disease Activity Index. Mononuclear cells and polymorphonuclear neutrophils were isolated from SLE patients and P-glycoprotein expression was measured using the relative fluorescence index and percentage of positive cells. The chi-square test was used to compare P-glycoprotein activity between responders and non-responders. Thirty-two patients with a mean age of 45.4 ± 10.7 years were included: 34.4% had a response to methotrexate and 65.6% did not. Mean relative fluorescence units of both mononuclear cells and polymorphonuclear neutrophils were significantly lower in patients with a good response (7.0 ± 4.3 vs. 9.6 ± 3.8; p = 0.041 and 4.2 ± 3.5 vs. 7.6 ± 4.0; p = 0.004). The prevalence of low fluorescence levels (<6 relative fluorescence units), signifying higher P-glycoprotein activity of both mononuclear cells and polymorphonuclear neutrophils, was higher in methotrexate responders than in non-responders (27.3 vs. 4.8%; p = 0.10 and 81.8 vs. 23.8%; p = 0.003, respectively). In SLE patients with joint involvement treated with methotrexate, P-glycoprotein activity was higher in responders to methotrexate than in non-responders. Further studies are required to determine the mechanisms behind this finding and whether P-glycoprotein activity mediates alterations in methotrexate efficacy.

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Acknowledgments

The authors would like to thank all patients who participated in this study for their patience and understanding.

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Benemérita Universidad Autόnoma de Puebla, Puebla, México

    Mario García-Carrasco & Claudia Mendoza-Pinto

  2. Systemic Autoimmune Diseases Research Unit, HGR 36-CIBIOR, Instituto Mexicano del Seguro Social, Av. 10 Poniente 2721, Amor, 72090, Puebla, Puebla, Mexico

    Mario García-Carrasco, Claudia Mendoza-Pinto, Salvador Macías-Díaz, Ivet Etchegaray-Morales, Pamela Soto-Santillán & Erick A. Jiménez-Herrera

  3. Department of State Research, Research Unit, Instituto Mexicano del Seguro Social, Puebla, México

    Socorro Méndez-Martínez

  4. Laboratorios Clínicos de Puebla, Puebla, México

    Beatriz Pérez-Romano, Omar Guzmán-Ruiz & Alejandro Ruiz-Argüelles

  5. Department of Chemistry and Biology, School of Sciences, Universidad de las Américas Puebla, Puebla, México

    Alejandro Ruiz-Argüelles

Authors
  1. Mario García-Carrasco
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  2. Claudia Mendoza-Pinto
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  3. Salvador Macías-Díaz
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  7. Beatriz Pérez-Romano
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  8. Erick A. Jiménez-Herrera
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  9. Omar Guzmán-Ruiz
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  10. Alejandro Ruiz-Argüelles
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Corresponding author

Correspondence to Claudia Mendoza-Pinto.

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García-Carrasco, M., Mendoza-Pinto, C., Macías-Díaz, S. et al. Clinical relevance of P-glycoprotein activity on peripheral blood mononuclear cells and polymorphonuclear neutrophils to methotrexate in systemic lupus erythematosus patients. Clin Rheumatol 36, 2267–2272 (2017). https://doi.org/10.1007/s10067-017-3728-0

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  • DOI: https://doi.org/10.1007/s10067-017-3728-0

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