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.

Keywords: IgE; c-kit; eosinophilic chronic rhinosinusitis; mast cell.

Figure 1

Histological findings of non-chronic rhinosinusitis (CRS), CRS, and eosinophilic chronic rhinosinusitis (ECRS). Hematoxylin and eosin staining at 400× magnification (high-powered field, HPF). (A) non-CRS, (B) CRS with no visible NP in the middle meatus (CRSsNP), (C) non-ECRS, (D) mild ECRS, (E) moderate ECRS, and (F) severe ECRS. In ECRS, infiltration of eosinophils under the mucosa was observed.

Figure 2

Immunohistochemical staining of c-kit in the diseased tissue. (A) non-CRS, (B) CRSsNP, (C) non-ECRS, (D) mild ECRS, (E) moderate ECRS, and (F) severe ECRS. The surface membrane of mast cells was positive for c-kit (400× magnification).

Figure 3

Lesion infiltration by c-kit-positive cells and the number of c-kit-positive cells. (A) Examination of the number of c-kit positive cells in the hotspot of each case. The number of c-kit-positive cells increased in the nasal polyp groups (p < 0.0001, Kruskal–Wallis test). Relationship between the number of c-kit positive cells and the preoperative CT score (B), eosinophil ratio in peripheral blood (C), and total serum IgE level (D).

Figure 4

Immunohistochemical findings of IgE in the diseased tissue. (A) non-CRS, (B) CRSsNP, (C) non-ECRS, (D) mild ECRS, (E) moderate ECRS, and (F) severe ECRS. IgE-positive cells increased in the diseased tissue (400× magnification).

Figure 5

Lesion infiltration by membrane IgE-positive cells and the number of IgE-positive cells. (A) Determination of membrane IgE-positive cell number in the hotspot of each case. The number of membrane IgE-positive cells increased in the nasal polyp groups (p < 0.0025, Kruskal–Wallis test). Relationships between the number of membrane IgE-positive cells and the preoperative CT score (B), eosinophil ratio in peripheral blood (C), and total serum IgE level (D).

Figure 6

Lesion infiltration by cytoplasmic IgE-positive cells in each lesion. (A) non-CRS, (B) CRSsNP, (C) non-ECRS, (D) mild ECRS, (E) moderate ECRS, and (F) severe ECRS. (G) Cytoplasmic IgE-positive mast cells were significantly increased in moderate and severe ECRS lesions (p < 0.05 and p < 0.01, respectively). Relationships between the number of cytoplasmic IgE-positive cells and the preoperative CT score (H), eosinophil ratio in peripheral blood (I), and total serum IgE level (J).

Figure 6

Lesion infiltration by cytoplasmic IgE-positive cells in each lesion. (A) non-CRS, (B) CRSsNP, (C) non-ECRS, (D) mild ECRS, (E) moderate ECRS, and (F) severe ECRS. (G) Cytoplasmic IgE-positive mast cells were significantly increased in moderate and severe ECRS lesions (p < 0.05 and p < 0.01, respectively). Relationships between the number of cytoplasmic IgE-positive cells and the preoperative CT score (H), eosinophil ratio in peripheral blood (I), and total serum IgE level (J).