The Expression And Clinical Significance Of Macrophage Migration Inhibitory Factor In CRSwNP Patients

Objective: Macrophage migration inhibitory factor(MIF),a multipotent inflammatory cytokine,has a role in inflammatory and autoimmune disease pathogenesis across disease initiation and progression.Chronic rhinosinusitis with nasal polyps(CRSwNP)is a highly heterogeneous inflammatory disease of the nasal sinuses,and MIF may also play an important role in the development and progression of CRSwNP.The present study is intended to explore the expression and clinical significance of MIF in patients with CRSwNP using clinical serum specimens,pathological tissue and case data.Methods: Forty healthy control(HC)patients,40 patients with chronic sinusitis without nasal polyps(CRSs NP),and 120 patients with CRSwNP were included.The 120 patients with CRSwNP included 51 patients with eosinophilic CRSwNP(e CRSwNP)and 69 patients with non-eosinophilic CRSwNP(ne CRSwNP).Preoperatively,venous serum was collected and serum MIF levels of all patients were measured by enzyme-linked immunosorbent assay(ELISA).The differences in clinical data and serum MIF levels between different groups of patients were compared,and the correlation between patients’ clinical data and their serum MIF levels was analyzed.The predictive value of serum MIF on CRSwNP endotype was assessed using receiver operating characteristic(ROC)curves and multivariate logistic regression analysis.Specimens of nasal polyps from some patients with CRSwNP(including e CRSwNP,ne CRSwNP)and nasal mucosa from patients with HC were sampled.Quantitative reverse transcription PCR(qRT-PCR),western blotting(WB)and immunofluorescence(IF)were used to detect MIF in different groups of patients.The expression levels of MIF in nasal polyps and nasal mucosa tissues were measured in different groups of patients,and the differences in tissue MIF levels were compared between different groups of patients.Results: Serum MIF levels was significantly higher in the CRSwNP group than in the CRSs NP and HC groups(P < 0.05),and in the e CRSwNP group than in the ne CRSwNP group(P = 0.006).Elevated serum MIF expression levels were associated with blood eosinophil count(r = 0.411,P < 0.001),blood eosinophil percentage(r = 0.377,P < 0.001),visual analog scale score(r = 0.204,P = 0.025),tissue eosinophil count(r= 0.705,P < 0.001),and tissue eosinophil percentage(r = 0.671,P <0.001)in patients with CRSwNP were significantly correlated.the ROC curve showed that serum MIF was a good preoperative predictor of CRSwNP endotype(AUC= 0.925,P < 0.001).Multivariate regression analysis showed that serum MIF was an independent factor associated with CRSwNP endotype.Meanwhile,the tissue MIF mRNA expression levels were significantly higher in the CRSwNP group than in the HC group by q RT-PCR(P < 0.05).In addition,the tissue MIF m RNA and protein expression levels were significantly higher in the e CRSwNP group than in the ne CRSwNP group,and statistically different(P < 0.05).IF results showed that the fluorescence expression intensity of MIF protein in CRSwNP tissues was significantly higher than that in the CRSs NP and HC groups,and the expression was more pronounced in e CRSwNP.Conclusion: 1.This study was the first to find that MIF expression was upregulated in the serum of patients with CRSwNP and closely correlated with disease severity,circulation and tissue eosinophilic inflammation in patients;serum MIF may be a potential biomarker for preoperative identification of CRSwNP endotype.2.MIF expression was upregulated in the tissues of CRSwNP patients and closely correlated with tissues endotype,further suggesting an important role of MIF in the development of disease and tissue eosinophilic inflammation in CRSwNP.