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

Abstract

Background: Macrophage migration inhibitory factor (MIF) is described as a pro-inflammatory cytokine involved in many inflammatory and allergic disorders, but the role of MIF in allergic rhinitis (AR) remains poorly clarified. The aim of this study was to investigate the association between circulating MIF levels and house dust mite (HDM)-induced AR, and evaluate MIF as a potential biomarker in reflecting disease severity and predicting the clinical response of sublingual immunotherapy (SLIT) in HDM-induced AR patients.Methods: In this study, we enrolled 160 persistent HDM-induced AR patients (AR group), including 48 mild AR patients (MAR group) and 112 moderate–severe AR patients (MSAR group), and 77 healthy controls (HC group). Circulating levels of MIF were measured by ELISA, and the relationship between MIF concentrations and disease severity was assessed. In the MSAR group, 106 patients were assigned to receive SLIT for 3 years. At the end of the study, patients were categorized into good response group and poor response group, and associations between clinical variables or biomarkers and clinical response were analyzed by the multivariate regression analysis.Results: The concentrations of serum MIF were significantly higher in AR patients than in HCs, especially in those with MSAR. Moreover, circulating MIF levels were positively correlated with TNSS, VAS, serum HDM–specific IgE, total IgE, blood eosinophil count, and blood eosinophil percentage (all p < 0.05). Eighty MSAR patients finally completed SLIT, 45 patients obtained good response, and 35 patients resulted in poor response. The serum levels of MIF were significantly lower in the good-response group than in the poor-response group (p < 0.001). The receiver operating characteristic analysis for MIF showed good accuracy for predicting clinical response of SLIT (area under the curve = 0.877, p < 0.001). The multivariate regression analysis demonstrated that serum MIF was an independent factor for SLIT responsiveness.Conclusion: Serum MIF appeared to be an important biological indicator in reflecting disease severity and an independent predictor for clinical responsiveness of SLIT in HDM-induced AR patients.

Macrophage migration inhibitory factor contributes to immunopathogenesis during Plasmodium yoelii 17XL infection

“…In addition, MIF regulates glucocorticoid immunosuppressive effects (Leng et al, 2009) and supports and enhances macrophage proinflammatory functions by preventing p53-mediated apoptosis (Roger et al, 2001). These findings explain how MIF plays an important role in the pathogenesis of several inflammatory disorders, such as sepsis (Pohl et al, 2017), inflammatory bowel disease (IBD) (Nishihira and Mitsuyama, 2009), allergic (Xie et al, 2021) rheumatoid arthritis and lupus (Bilsborrow et al, 2019). Moreover, MIF is also involved in the protection of several parasitic infections (Rosado Jde and Rodriguez-Sosa, 2011;Filbey et al, 2019), such as Taenia crassiceps (Rodriguez-Sosa et al, 2003), Toxoplasma gondii (Terrazas et al, 2010), and Trypanosoma cruzi (Fu et al, 2012a).…”

Mechanisms and biomarkers of successful allergen-specific immunotherapy

“…The leptin concentration in serum and nasal lavage was significantly decreased after SLIT treatment in 40 HDM-AR patients without obesity [ 129 ]. The macrophage migration inhibitory factor (MIF) is a T-lymphocyte-derived protein and the serum concentrations of MIFs were significantly lower in HDM-induced AR patient’s good-response sublingual AIT group than in the poor-response group [ 130 ].…”

MIF is essential to the establishment of house dust mite‐induced airway inflammation and tissue remodeling in mice

“…MIF is a pleotropic molecule that exerts a proinflammatory activity on several diseases such as sepsis, esophagitis, cancer, infections, and allergies [11][12][13][14][15][16][17]. Clinical studies demonstrated that asthmatic patients present higher MIF concentrations in the BALF, sputum, and serum than healthy controls [9,14].…”