Background Previous studies have reported that methotrexate is effluxed from cells by several transmembrane proteins, including P glycoprotein (P-gp). Moreover, various studies have examined the relationship between disease activity and P-gp expression levels/function in systemic lupus erythematosus (SLE) patients. Nonetheless, the role of P-gp activity in SLE patients receiving methotrexate has not previously been evaluated.
Objectives To investigate the relationship between P-gp activity on peripheral blood leukocytes from SLE patients with lupus arthritis and clinical response to methotrexate.
Methods Mononuclear cells (MNC) and polymorphonuclear neutrophils (PMN) were isolated from SLE patients (≥4 of the ACR classification criteria) with joint manifestations who had received methotrexate and corticosteroids (≥15 mg). Methotrexate responders and non-responders were compared according to the Clinical Disease Activity Index (CDAI) score. A flow cytometric daunorrubicin- efflux assay was made in peripheral blood leukocytes to determine the P-gp activity.
Results Thirty-two patients were included: 34.4% had responded to methotrexate and 65.6% had not. The mean relative fluorescence unit (RFU) of both MNC and PMN were significantly lower in patients with a good response compared with those without good response (7.0±4.3 vs. 9.6±3.8; p=0.4 and 4.2±3.5 vs. 7.6±4.0; p=0.004. The prevalence of low fluorescence levels (<5 RFU), which signifies higher P-gp activity of both MNC and PMNC was higher in methotrexate responders compared to non-responders, 27.3% vs. 4.8% (p=0.10) and 81.8% vs. 23.8% (p=0.003), respectively.
Conclusions In patients with SLE, P-gp activity with clinical response to oral methotrexate treatment led to down P-gp activity. Further studies are required to determine the mechanisms behind this finding and whether P-gp activity mediates alterations in the efficacy of methotrexate.
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Acknowledgements We would like to thank David Buss for his valuable guidance and advice during this project.
Disclosure of Interest None declared