Cao P-P, Zhang Y-N, Liao B, Ma J, Wang B-F, Wang H, Zeng M, Liu W-H, Schleimer R P, Liu Z
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Clin Exp Allergy. 2014;44(5):690-700. doi: 10.1111/cea.12304.
Eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) display distinct patterns of inflammation. However, the pathogenic mechanisms underlying the heterogeneity of CRSwNP need further investigation.
To investigate local immunoglobulin E (IgE) production and phenotype of mast cells in eosinophilic and non-eosinophilic CRSwNP in Chinese.
Total and specific IgE levels were analysed by means of the ImmunoCAP system. The molecular steps involved in class-switch recombination to IgE were investigated using RT-PCR assays. Mast cell phenotypes, IgE- and high-affinity IgE receptor (FcεRI)-positive cells, and allergen binding to specific IgE in sinonasal mucosa were determined by means of immunohistochemistry.
Compared with controls and non-eosinophilic CRSwNP, local total IgE levels were increased, and local specific IgE to common aeroallergens was more frequently found, in Chinese eosinophilic CRSwNP independent of atopy and without significant association with Staphylococcus aureus enterotoxins. The ε germline gene transcript was also more frequently detected in eosinophilic CRSwNP. The number of IgE- and FcεRI-positive cells was increased in eosinophilic CRSwNP. Most IgE- and FcεRI-positive cells were mast cells. Dust mite antigens could bind to IgE on mast cells in situ. The number of mast cells positive for both tryptase and chymase and activated mast cells was increased in eosinophilic CRSwNP and the number of activated mast cells positively correlated with local IgE level, eotaxin-1 level, and eosinophil count in CRSwNP.
The local IgE induced by common aeroallergens may mediate mast cell activation and contribute to subsequent eosinophilic inflammation in Chinese CRSwNP. This study offers a rationale for considering intervention strategies designed to target 'local allergy' in eosinophilic CRSwNP.
嗜酸性粒细胞性和非嗜酸性粒细胞性慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)表现出不同的炎症模式。然而,CRSwNP异质性的致病机制需要进一步研究。
研究中国嗜酸性粒细胞性和非嗜酸性粒细胞性CRSwNP中局部免疫球蛋白E(IgE)的产生及肥大细胞表型。
采用免疫捕获系统分析总IgE和特异性IgE水平。使用逆转录-聚合酶链反应(RT-PCR)检测法研究参与IgE类别转换重组的分子步骤。通过免疫组织化学确定肥大细胞表型、IgE和高亲和力IgE受体(FcεRI)阳性细胞以及变应原与鼻窦黏膜中特异性IgE的结合情况。
与对照组和非嗜酸性粒细胞性CRSwNP相比,在中国嗜酸性粒细胞性CRSwNP中,局部总IgE水平升高,更常发现针对常见气传变应原的局部特异性IgE,与特应性无关,且与金黄色葡萄球菌肠毒素无显著关联。在嗜酸性粒细胞性CRSwNP中也更常检测到ε种系基因转录本。嗜酸性粒细胞性CRSwNP中IgE和FcεRI阳性细胞数量增加。大多数IgE和FcεRI阳性细胞为肥大细胞。尘螨抗原可原位结合肥大细胞上的IgE。嗜酸性粒细胞性CRSwNP中同时表达类胰蛋白酶和糜蛋白酶的肥大细胞数量及活化肥大细胞数量增加,且CRSwNP中活化肥大细胞数量与局部IgE水平、嗜酸性粒细胞趋化因子-1水平及嗜酸性粒细胞计数呈正相关。
常见气传变应原诱导的局部IgE可能介导肥大细胞活化,并导致中国嗜酸性粒细胞性CRSwNP随后的嗜酸性粒细胞炎症。本研究为考虑针对嗜酸性粒细胞性CRSwNP中“局部过敏”的干预策略提供了理论依据。