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 6months 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 (78.02ng/mL±114.11 vs. 33.75ng/mL±41.11; p=0.018) or versus reference group subjects (30.56ng/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.