Assessment of serum macrophage migration inhibitory factor (MIF), adiponectin, and other adipokines as potential markers of proteinuria and renal dysfunction in lupus nephritis: a cross-sectional study

Abstract

Background To date, the association of serum macrophage migration inhibitory factor (MIF) and serum adipokines with lupus nephritis is controversial. Objective To assess the utility of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritis. Methods Cross-sectional study including 196 systemic lupus erythematosus (SLE) patients and 52 healthy controls (HCs). Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal SLE involvement was investigated by renal-SLEDAI. MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed the correlations of quantitative variables by Spearman correlation (rs). Multivariable linear regression adjusted the variables associated with the severity of proteinuria. Results SLE patients had higher MIF (p = 0.02) and adiponectin (p < 0.001) than HCs. Patients with renal SLE involvement (n = 43) had higher adiponectin (19.0 vs 13.3 μg/mL, p = 0.002) and resistin (10.7 vs 8.9 ng/mL, p = 0.01) than patients with non-renal SLE (n = 153). Proteinuria correlated with high adiponectin (rs = 0.19, p < 0.009) and resistin (rs = 0.26, p < 0.001). MIF (rs = 0.27, p = 0.04). Resistin correlated with increased creatinine (rs = 0.18, p = 0.02). High renal-SLEDAI correlated with adiponectin (rs = 0.21, p = 0.004). Multiple linear regression showed that elevated adiponectin (p = 0.02), younger age (p = 0.04) and low MIF (p = 0.02) were associated with the severity of proteinuria. Low MIF and high adiponectin levels interacted to explain the association with the severity of proteinuria (R2 = 0.41). Conclusions High adiponectin combined with low MIF concentrations int+eract to explain the severity of proteinuria in renal SLE. These findings highlight the relevance of adiponectin, resistin and MIF as markers of LN.

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite–Induced Allergic Rhinitis

“…A recent study observed that MIF amounts were increased in the allergen-induced skin tissue of atopic dermatitis murine models, and the elevated MIF levels promoted the secretion of IL-4 and IL-5, and eosinophil recruitment in the skin (Yoshihisa et al, 2011). Gamez-Nava and colleagues found that levels of MIF were higher in the serum of lupus nephritis patients than levels of MIF in that of HCs and positively correlated with the severity of proteinuria and renal dysfunction (Gamez-Nava et al, 2020). Although MIF is known as an important pro-inflammatory cytokine, the role of MIF in AR remains elusive.…”

“…Macrophage inhibitory factor (MIF), a T lymphocyte-derived protein, is a pleiotropic inflammatory cytokine which is expressed in various cell types, including macrophages, T lymphocyte cells, eosinophils, and neutrophils (Zhao et al, 2019a;Bilsborrow et al, 2019;Gamez-Nava et al, 2020). Accumulating evidence showed that MIF exhibited a variety of biological functions in the inflammation and immune response, and was closely involved in allergic and autoimmune diseases (Yoshihisa et al, 2011;Bozza et al, 2020;Li et al, 2021).…”

“…Accumulating evidence showed that MIF exhibited a variety of biological functions in the inflammation and immune response, and was closely involved in allergic and autoimmune diseases (Yoshihisa et al, 2011;Bozza et al, 2020;Li et al, 2021). Previous studies demonstrated that the concentrations of MIF in serum and local tissue were significantly elevated in asthma (Lan et al, 2020;Li et al, 2021), atopic dermatitis (Yoshihisa et al, 2011), rheumatoid arthritis (Bilsborrow et al, 2019), and systemic lupus erythematosus (Gamez-Nava et al, 2020). Thus, it is reasonable to assume that MIF might also play an important role in the pathogenesis of AR.…”