The Relationship Between Local IgE In Tissue And Eosinophilic Chronic Rhinosinusitis With Nasal Polyps

PART I The Relationship and Clinical Significance between Local Total IgE、Specific IgE in Tissue and Eosinophilic Chronic Rhinosinusitis with Nasal PolypsBackground:Eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP)exhibits a poorer prognosis than neCRSwNP.The aim of this study was to analyze the potential of total immunoglobulin E(IgE)and specific IgE(sIgE)levels in tissues for distinguishing and assessing eCRSwNP.Methods:We enrolled 10 control and 88 CRSwNP patients.The clinical data of patients were collected before surgery.Nasal mucosa tissues were taken during surgery for measurements of total IgE,sIgE(weed pollen,epidermal and animal protein,mold,house dust,tree pollen)and subepithelial eosinophil counts.The predictive significance of potential predictors for eCRSwNP was assessed with receiver operating characteristic(ROC)curves.Results:Nasal polyps total IgE and mold-sIgE were positively correlated with blood and tissue eosinophils,comorbid allergic rhinitis and asthma,ethmoid/maxillary sinus total score(E/M ratio),visual analog scale(VAS)and CT score.The ROC curve analysis showed that tissue total IgE(p=0.0004),mold-sIgE(p=0.003),blood eosinophil percentage(p=0.0003)and absolute blood eosinophil count(p=0.001)acted as predictive factors for eCRSwNP.According to the cutoff value of the tissue total IgE of 34.55 KU/L,patients of high levels were more likely to develop asthma(p=0.016)and had significantly higher eosinophil counts(p=0.022),eosinophil percentage(p=0.029)and total IgE(p=0.002)in blood.Conclusion:Tissue total IgE and mold-sIgE had a significant relationship with the clinical and pathological characteristics of CRSwNP patients and might be reliable for distinguishing and assessing eCRSwNP.PART Ⅱ The Investigation of the Function and Mechanism of Differentially Expressed mRNAs between Eosinophilic Nasal Polyps with Different Expression levels of Total IgEBackground:Eosinophils in peripheral blood and nasal polyps were significantly elevated in patients of eCRSwNP than neCRSwNP,but the total IgE was not necessarily elevated.This study aimed to identify differential gene expression from eCRSwNP patients with different levels of IgE expression,to identify IgE-related transcriptomic signatures that can help identify disease targets and select new treatments.Methods:mRNA transcriptome sequencing was performed on nasal mucosa from 18 eosinophilic nasal polyps with high expression of IgE(High group)and 12 with low expression(Low group)and from 10 control subjects.Immunohistochemical staining was used to analyze the differential genes and different cell types.Results:Patients in the High group were positively correlated with VAS score(p=0.016),comorbid asthma(p=0.030).Among them,the significantly up-regulated genes in the High group include PIP,IGHG4,ITLN1,CXCL5,TCN1,LTF,SPDEF,KRT1,CD27,CST1,IL19,and the significantly down-regulated genes include IL11,TNF,CXCR1,CXCL3,CCL15,CCL20.Through Gene Ontology(GO)enrichment analysis,it was found that biological processes such as tissue homeostasis,antimicrobial humoral response,humoral immune response were up-regulated in the High group;the cellular components of up-regulated genes were mainly secretory granule lumen.At the same time,compared with the Low group,the High group mainly showed the downregulation of ciliary function and microtubule-related protein function.The same results were preliminarily verified by immunohistochemical staining.Conclusion:IgE high-expressed eCRSwNP exhibited different transcriptomic signatures from the IgE low-expressed.The expression of IgG4 in eCRSwNP was increased,the function of ciliated cells was decreased,and the function of glandular cells(ITLN1 and TCN1)was increased,which may be closely related to the high expression of IgE in nasal polyps.