The role of serum macrophage migration inhibitory factor in preoperative prediction of chronic rhinosinusitis with nasal polyps endotypes

Highlights

• Serum MIF levels were elevated in CRSwNP patients, especially in eCRSwNP patients.

• Serum MIF was a specific biomarker for distinguishing CRSwNP endotypes.

• Serum MIF levels were closely associated with mucosal eosinophil infiltration.

Abstract

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease and can be categorized into eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). Exploring effective biomarkers to distinguish endotypes is important for personalized therapies. The present study aims to evaluate the predictive value of serum MIF in CRSwNP endotypes.

Methods

One hundred and twenty CRSwNP patients, including 51 eCRSwNP and 69 neCRSwNP, 40 chronic rhinosinusitis without nasal polyps (CRSsNP) patients and 40 healthy controls (HC) were enrolled. Serum MIF levels were determined by enzyme-linked immunosorbent assay (ELISA). The patients’ clinical variables were analyzed for correlations with serum MIF. Receiver operating characteristic (ROC) curve and multivariate analysis were utilized to assess the predictive value of serum MIF in CRSwNP endotypes.

Results

The serum MIF levels were significantly higher in CRSwNP group than CRSsNP group and HC group (P < 0.001), and the serum MIF levels were increased in eCRSwNP compared to neCRSwNP group (P = 0.006). Elevated serum MIF levels were significantly correlated with blood eosinophil (B-EOS) count (r = 0.411, P < 0.001), B-EOS percentage (r = 0.377, P < 0.001), visual analog scale score (r = 0.204, P = 0.025), tissue eosinophil (T-EOS) count (r = 0.705, P < 0.001) and T-EOS percentage (r = 0.671, P < 0.001) in CRSwNP patients. ROC curve demonstrated that serum MIF exhibited good preoperative prediction in CRSwNP endotypes (area under the curve = 0.925, P < 0.001). Multivariate regression analysis showed that serum MIF was an independent factor associated with CRSwNP endotypes.

Conclusions

This was the first study identifying serum MIF as a possible specific biomarker for preoperatively distinguishing CRSwNP endotypes. Furthermore, the serum MIF levels were found to be closely associated with the degree of mucosal eosinophil infiltration.

Introduction

Chronic rhinosinusitis (CRS), characterized by nasal discharge, nasal obstruction, facial pain, and reduction of smell, is one of the most prevalent chronic diseases [1]. Based on presence of nasal polyp, CRS is categorized into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP)[2], [3]. CRSwNP is a highly heterogeneous disease, and it is further grouped into eosinophilic CRSwNP (eCRSwNP) or non-eosinophilic CRSwNP (neCRSwNP) according to the degree of infiltrating eosinophils in the tissue [4], [5]. In comparison with neCRSwNP, eCRSwNP exhibiteds more serious disease symptoms, poorer prognosis and a higher rate of reoccurrence because of its distinct inflammatory pathways and pathophysiological mechanisms [6], [7], [8]. Given that distinguishing CRSwNP subtypes before surgery was pivotal to achieve personalized treatments and improve follow-up protocols. However, there is a lack of simple and accurate biomarkers currently available in identify these endotypes during clinical practice. Therefore, identifying specific biomarkers with high accuracy and reliability for distinguishing CRSwNP endotypes is urgently needed.

Macrophage migration inhibitory factor (MIF) is a multi-effect pro-inflammatory factor, which expressed in a variety of cells, such as monocytes, macrophages, eosinophils, neutrophils, B cells and T cells [9], [10]. Growing evidences have demonstrated that MIF exhibited important biological functions in promoting inflammatory response, antagonizing glucocorticoid effect and mediating the release of pro-inflammatory factors [11], [12], [13]. Moreover, MIF also has been suggested to affect eosinophil physiology, including promoting eosinophil differentiation, activation, migration and survival [11], [14], and be closely involved in the pathogenesis of various inflammatory diseases, including allergic rhinitis [15], inflammatory bowel disease [16], asthma [17], eosinophilic esophagitis [18], and atopic dermatitis[19]. Thus, it is reasonable to assume that MIF might also act an important role in the pathogenesis of CRSwNP, and contribute to distinguishing its endotypes.

In this study, we aimed to investigate the changes of serum MIF levels in CRSwNP patients, and evaluated the predictive value of serum MIF levels in CRSwNP endotypes.