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 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.

Association of Platelet Binding to Lymphocytes with B Cell Abnormalities and Clinical Manifestations in Systemic Lupus Erythematosus

“…SLE patients with albumin/creatinine levels > 2.5 mg/mmol showed higher percentages of CD19+PLT+, CD4+PLT+, and CD8+PLT+ than those with normal levels (≤2.5 mg/mmol) (Figure 5(d)). SLE patients with SLEDAI > 3 (patients with active disease suggestive of treatment change) [39, 40] showed higher percentages of CD19+PLT+, CD4+PLT+, and CD8+PLT+ than those with a SLEDAI ≤ 3 (CD19+PLT+: 8.51 ± 0.57 for >3 vs. 6.43 ± 0.49 for ≤3, p = 0.02; CD4+PLT+: 9.73 ± 0.66 for >3 vs. 7.11 ± 0.64 for ≤3, p = 0.02; and CD8+PLT+: 9.49 ± 0.59 for >3 vs. 7.22 ± 0.6 for ≤3, p = 0.03). Comparable percentages of each subpopulation of lymphocytes with bound platelets were observed when SLE patients were segregated according to medication and cutaneous or articular manifestations (data not shown).…”

Glucocorticoids—All-Rounders Tackling the Versatile Players of the Immune System

“…P-gp is widely expressed in a variety of tissues, including peripheral blood T and B lymphocytes (156). However, P-gp expression is increased in these cells in SLE patients and is correlated with disease activity (157). Thus, elevated levels of P-gp lead to poor disease control by systemic glucocorticoid therapy and are associated with glucocorticoid resistance (157, 158).…”

“…However, P-gp expression is increased in these cells in SLE patients and is correlated with disease activity (157). Thus, elevated levels of P-gp lead to poor disease control by systemic glucocorticoid therapy and are associated with glucocorticoid resistance (157, 158). Beside P-gp, the inflammatory cytokine macrophage MIF actively reduces glucocorticoid action, participates in multiple stages of the inflammatory response and is widely associated with autoimmune disorders such as RA and SLE (159).…”

ABCB1 gene polymorphisms impact the effect of high‐dose intravenous methylprednisolone therapy on optic neuritis associated with AQP4‐IgG ‐positive neuromyelitis optica spectrum disorder

“…P‐gp is expressed in some tumours and nonmalignant tissues (intestine, blood–brain barrier) and functions as an efflux pump that transports natural compounds and therapeutic agents via ATP hydrolysis to protect cells from a variety of endogenous and exogenous toxins. P‐gp has been reported to be associated with resistance to a variety of drugs, including GCs 11,12 …”