Allergy & Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, and the Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom; Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden.
Institute of Immunology, Hannover Medical School, Hannover, Germany.
J Allergy Clin Immunol. 2019 Jun;143(6):2086-2094.e2. doi: 10.1016/j.jaci.2019.02.001. Epub 2019 Feb 11.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by local production of polyclonal IgE idiotypes. Although tissue IgE concentrations can be in the range of several thousand kilounits per liter, the regulatory mechanisms by which IgE-mediated inflammation is controlled in patients with nasal polyps are not well understood.
We sought to determine whether locally induced IgG antibodies in patients with nasal polyps can inhibit an IgE-mediated proallergic response.
Nasal polyp homogenates were collected from patients with grass pollen allergy with CRSwNP and nonallergic control subjects. IgE levels were measured using the Immuno Solid-phase Allergen Chip assay. IgE-containing nasal polyp homogenates with or without IgG depletion were evaluated for their capacity to promote IgE-facilitated allergen presentation, basophil activation, and histamine release. Local IgE and IgG repertoires were evaluated using Immunoglobulin 454 sequencing.
We show that IgG plays a key role in controlling IgE-mediated inflammatory responses in patients with nasal polyps. Depletion of IgG from nasal homogenates resulted in an increase in CD23-mediated IgE-facilitated allergen binding to B cells but also enhanced FcεRI-mediated allergen-driven basophil activation and histamine release. A similar response was observed in relation to specific IgE antibodies to Staphylococcus aureus enterotoxins. The capacity of IgG in nasal polyps to limit IgE-mediated inflammation is based on the fact that IgG repertoires widely share the antigen targets with the IgE repertoires in both allergic and nonallergic subjects.
Polyclonal IgE idiotypes in patients with CRSwNP are functional, promote IgE-mediated proallergic inflammation, and are partially antagonized by corresponding IgG idiotypes. This is most likely due to the fact that IgE and IgG clonotypes are widely shared in patients with nasal polyps.
伴有鼻息肉的慢性鼻-鼻窦炎（CRSwNP）常表现为局部产生多克隆 IgE 独特型。尽管组织 IgE 浓度可达到几千千单位/升，但对于鼻息肉患者中 IgE 介导的炎症是如何受到调控的，其机制尚不清楚。
我们旨在确定鼻息肉患者中诱导产生的局部 IgG 抗体是否能抑制 IgE 介导的过敏反应。
收集伴有花粉过敏的 CRSwNP 患者和非过敏对照患者的鼻息肉匀浆，采用 Immuno Solid-phase Allergen Chip assay 检测 IgE 水平。评估含有 IgE 的鼻息肉匀浆在有无 IgG 耗尽的情况下，是否具有促进 IgE 辅助变应原呈递、嗜碱性粒细胞激活和组胺释放的能力。采用 Immunoglobulin 454 测序评估局部 IgE 和 IgG 库。
我们发现 IgG 在控制鼻息肉患者 IgE 介导的炎症反应中起着关键作用。从鼻匀浆中耗尽 IgG 会导致 CD23 介导的 IgE 辅助变应原与 B 细胞的结合增加，但也增强了 FcεRI 介导的变应原驱动的嗜碱性粒细胞激活和组胺释放。在与金黄色葡萄球菌肠毒素的特异性 IgE 抗体相关时，也观察到类似的反应。鼻息肉中 IgG 限制 IgE 介导炎症的能力基于以下事实：在过敏和非过敏患者中，IgG 库广泛共享与 IgE 库相同的抗原靶标。
伴有 CRSwNP 的患者的多克隆 IgE 独特型具有功能，可促进 IgE 介导的过敏前炎症，并被相应的 IgG 独特型部分拮抗。这很可能是由于鼻息肉患者的 IgE 和 IgG 克隆型广泛共享。
