Steroid Resistance Associated with High MIF and P-gp Serum Levels in SLE Patients

Abstract

Approximately 30% of patients with systemic lupus erythematosus (SLE) present steroid resistance (SR). Macrophage migration inhibition factor (MIF) and P-glycoprotein (P-gp) could be related to SR. This work aims to evaluate the relationship between MIF and P-pg serum levels in SR in SLE. Methods: Case−control study including 188 SLE patients who were divided into two groups (90 in the steroid-resistant group and 98 in the steroid-sensitive (SS) group) and 35 healthy controls. MIF and P-gp serum levels were determined by ELISA. Multivariable logistic regression and chi-squared automatic interaction detection (CHAID) were used to explore risk factors for SR. Results: The steroid-resistant group presented higher MIF and P-gp serum levels in comparison with the SS (p < 0.001) and reference (p < 0.001) groups. MIF correlated positively with P-gp (rho = 0.41, p < 0.001). MIF (≥15.75 ng/mL) and P-gp (≥15.22 ng/mL) were a risk factor for SR (OR = 2.29, OR = 5.27). CHAID identified high P-gp as the main risk factor for SR and high MIF as the second risk factor in those patients with low P-gp. Conclusions: An association between MIF and P-gp serum levels was observed in SR. CHAID identified P-gp ≥ 15.22 ng/mL as the main risk factor for SR. More studies are needed to validate these results.

Keywords: CHAID; MIF; P-gp; interaction; steroid-resistance; systemic lupus erythematosus.

Figure 1

Comparison of MIF and P-gp serum levels; (A) comparison of the MIF serum levels among study groups; (B) comparison of P-gp serum levels among study groups; (C) comparison of MIF serum levels by GCS doses; (D) comparison of P-gp serum levels by GCS doses. ****: p-value ≤ 0.00001; ***: p-value ≤ 0.001; **: p-value ≤ 0.01; *: p-value ≤ 0.05; ns = not significant. SS, Steroid Sensitive; SR, Steroid Resistant.

Figure 2

CHAID decision tree.