①背景：慢性鼻窦炎合并鼻息肉(CRSwNP)的特点是局部产生多克隆IgE亚型。虽然组织IgE的浓度可以达到几千KU/L，但是对于IgE介导的炎症在鼻息肉患者中的调控机制还不是很清楚。②方法：我们试图确定鼻息肉患者局部诱导的IgG抗体是否能够抑制IgE介导的促过敏反应。收集花粉过敏的慢性鼻窦炎合并鼻息肉（CRSwNP）患者和非过敏对照组的鼻腔息肉匀浆。采用免疫固相变应原芯片法测定IgE水平。我们评估了含有IgE 的鼻息肉匀浆(有或无IgG消耗)在促进IgE诱导的过敏原表达、嗜碱性细胞活化和组胺释放方面的能力。采用免疫球蛋白454测序法评价局部IgE和IgG谱。③结果：我们发现IgG在控制鼻息肉患者的IgE介导的炎症反应中起着关键作用。损耗鼻匀浆中的IgG，导致了 IgE-诱导的CD23-介导的过敏原与B细胞的结合量的增加，也增强FcεRI-介导的过敏原-驱动的嗜碱细胞激活和组胺释放。对金黄色葡萄球菌肠毒素特异性IgE抗体也有类似的反应。鼻息肉中IgG抑制IgE介导的炎症的能力是基于这样一个事实，即在过敏和非过敏受试者中，IgG与IgE谱之间存在广泛的共享抗原靶点。④结论：CRSwNP患者多克隆IgE亚型具有功能性，可促进IgE介导的过敏性炎症反应，并可被相应的IgG亚型部分拮抗。这很可能是由于IgE和IgG在鼻息肉患者中存在广泛共享的克隆型。
Broad IgG repertoire in patients with chronic rhinosinusitis with nasal polyps regulates proinflammatory IgE responses
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.
Mohamed H. Shamji Irene Thomsen Janice A. Layhadi Jasper Kappen Gabriële Holtappels Umit Sahiner Amy Switzer Stephen R. Durham Oliver Pabst