Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
J Allergy Clin Immunol. 2018 Nov;142(5):1489-1499.e23. doi: 10.1016/j.jaci.2018.07.025. Epub 2018 Aug 10.
Although upregulated expression of local IgD has been reported in patients with chronic rhinosinusitis (CRS), its function is unclear.
We sought to explore the expression and function of soluble IgD in patients with CRS, particularly CRS with nasal polyps.
IgD levels in sinonasal mucosa were analyzed by using RT-PCR and ELISA. Numbers and phenotypes of IgD cells were studied by means of immunohistochemistry, immunofluorescence, and flow cytometry. HMC-1 cells, a human mast cell line, and mast cells purified from eosinophilic polyps were cultured alone or with naive B cells purified from peripheral blood. The antigen specificity of nasal IgD was investigated by using ELISA.
The mRNA expression of immunoglobulin heavy constant delta gene, numbers of IgD cells, and protein levels of secretory IgD in sinonasal mucosa were increased in patients with CRS with or without nasal polyps compared with control subjects. Numbers of IgD plasmablasts were increased in both eosinophilic and noneosinophilic polyps, whereas numbers of IgD mast cells were only increased in eosinophilic polyps. Cross-linking IgD induced serum preincubated HMC-1 cells and polyp mast cells to produce B-cell activating factor, IL-21, IL-4, and IL-13 and to promote IgM, IgG, IgA, and IgE production from B cells. In eosinophilic polyps expression of those B cell-stimulating factors in mast cells and close contact between mast cells and B cells were found. Moreover, positive correlations of total IgD levels with total IgE levels and eosinophilia and upregulation of specific IgD against house dust mites were discovered in eosinophilic polyps.
IgD-activated mast cells can facilitate IgE production and eosinophilic inflammation in patients with CRS with nasal polyps.
尽管有报道称慢性鼻-鼻窦炎（CRS）患者局部 IgD 表达上调，但其功能尚不清楚。
我们旨在探讨 IgD 在 CRS 患者，尤其是伴有鼻息肉的 CRS 患者中的表达和功能。
通过 RT-PCR 和 ELISA 分析鼻黏膜中 IgD 水平。通过免疫组织化学、免疫荧光和流式细胞术研究 IgD 细胞的数量和表型。单独培养人肥大细胞系 HMC-1 细胞和从嗜酸性息肉中纯化的肥大细胞，或与从外周血中纯化的幼稚 B 细胞共培养。通过 ELISA 研究鼻 IgD 的抗原特异性。
与对照组相比，伴有或不伴有鼻息肉的 CRS 患者的免疫球蛋白重链 delta 基因 mRNA 表达、鼻黏膜 IgD 细胞数量和分泌型 IgD 蛋白水平均增加。嗜酸性和非嗜酸性息肉中 IgD 浆母细胞数量均增加，而仅在嗜酸性息肉中 IgD 肥大细胞数量增加。交联 IgD 可诱导血清预孵育的 HMC-1 细胞和息肉肥大细胞产生 B 细胞激活因子、IL-21、IL-4 和 IL-13，并促进 B 细胞产生 IgM、IgG、IgA 和 IgE。在嗜酸性息肉中发现，肥大细胞表达这些 B 细胞刺激因子，并与 B 细胞密切接触。此外，在嗜酸性息肉中还发现总 IgD 水平与总 IgE 水平和嗜酸性粒细胞增多呈正相关，并且对屋尘螨的特异性 IgD 上调。
IgD 激活的肥大细胞可促进伴有鼻息肉的 CRS 患者 IgE 产生和嗜酸性粒细胞炎症。
