Clinical Significance of Cytoplasmic IgE-Positive Mast Cells in Eosinophilic Chronic Rhinosinusitis

Abstract

Cross-linking of antigen-specific IgE bound to the high-affinity IgE receptor (FcεRI) on the surface of mast cells with multivalent antigens results in the release of mediators and development of type 2 inflammation. FcεRI expression and IgE synthesis are, therefore, critical for type 2 inflammatory disease development. In an attempt to clarify the relationship between eosinophilic chronic rhinosinusitis (ECRS) and mast cell infiltration, we analyzed mast cell infiltration at lesion sites and determined its clinical significance. Mast cells are positive for c-kit, and IgE in uncinated tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. The number of positive cells and clinicopathological factors were analyzed. Patients with ECRS exhibited high levels of total IgE serum levels and elevated peripheral blood eosinophil ratios. As a result, the number of mast cells with membranes positive for c-kit and IgE increased significantly in lesions forming NP. Therefore, we classified IgE-positive mast cells into two groups: membrane IgE-positive cells and cytoplasmic IgE-positive cells. The amount of membrane IgE-positive mast cells was significantly increased in moderate ECRS. A positive correlation was found between the membrane IgE-positive cells and the radiological severity score, the ratio of eosinophils, and the total serum IgE level. The number of cytoplasmic IgE-positive mast cells was significantly increased in moderate and severe ECRS. A positive correlation was observed between the cytoplasmic IgE-positive cells and the radiological severity score, the ratio of eosinophils in the blood, and the total IgE level. These results suggest that the process of mast cell internalization of antigens via the IgE receptor is involved in ECRS pathogenesis.

The Percentage of PNAd-Expressing Vessels is Correlated with Disease Severity in Eosinophilic Chronic Rhinosinusitis

“…Clinically, it is noteworthy that we found that the postoperative recurrence rate of severe ECRS was significantly higher than that of less severe ECRS (see Table 2). Gion et al recently compared characteristics of patients showing different ECRS severity, 21 and their observations were comparable to what we report here. For example, serum IgE levels, the proportion of eosinophils in peripheral blood, and comorbidity with asthma in severe ECRS were higher than those values seen in less severe ECRS.…”

International consensus statement on allergy and rhinology: rhinosinusitis 2021

“…Mast cells . Two studies showed that mast cells are significantly increased in NPs and primarily accumulate in the epithelium 822,823 1472 . Type 2 cytokines, IL‐5, IL‐13, and IL‐4, are secreted by mast cells, Th2 cells and group 2 ILCs 1473 and therefore mast cells may enhance Th2 inflammation 1469 …”

Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence

“…Here we have analyzed the inflammatory modulations due to dupilumab treatment, as well as modulation of miRNAs expression, to identify new prognostic biomarkers. It was well demonstrated that increased IgE and IL-8 concentrations may be found in patients with CRSwNP stimulating multiple inflammatory pathways [ 23 , 24 ]. Indeed, IL-8 plays a crucial role in the inflammatory processes acting as a chemotactic factor for neutrophils and lymphocytes, as angiogenic factor, as well as tumor progression [ 25 , 26 , 27 ], and an IL-8-dominant inflammatory profile is frequently found in patients with CRSwNP [ 28 , 29 ].…”